A Method of Estimating a Circulating Tumor DNA Burden and Related Kits and Methods

ABSTRACT

There is provided a method of estimating a circulating tumour DNA (ctDNA) burden/level in a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cell-free DNA (cfDNA) that maps to one or more nucleosome-depleted region (NDR); and estimating the ctDNA burden based on said level of cfDNA, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood tissue and tumour tissue and/or (ii) is degraded to different extents between healthy blood tissue and blood tissue of a tumour-bearing subject. Also provided are related kits and methods, in one embodiment, the one or more NDR comprises one or more NDR of SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG18L2, SHKBP1, BCAR1, RAB25 and LSR.

TECHNICAL FIELD

The present disclosure relates broadly to a method of estimating a disease burden, such as a circulating tumor DNA (ctDNA) burden, and related kits and methods.

BACKGROUND

Cell-free DNA (cfDNA) is present in the blood circulation of humans. In healthy individuals, the death of normal cells of the hematopoietic lineage is the main contributor of plasma cfDNA. In cancer patients, blood plasma can carry circulating tumor DNA (ctDNA) fragments originating from tumor cells, offering non-invasive access to somatic genetic alterations in tumors. The ctDNA profile of a cancer patient is clinically informative in at least two major ways. Firstly, the profile can provide information about specific actionable mutations that can guide therapy. Secondly, the profile can be used to infer tumor growth dynamics by estimating the amount of ctDNA in the blood. This latter information offers a promising non-invasive approach to track disease progression during clinical trials or therapy, offering a real-time tool to adjust therapy.

Existing next-generation sequencing-based approaches to estimate ctDNA levels in plasma samples are based on somatic single nucleotide variant allele frequencies (SNV VAFs), copy number aberrations (CNAs), or DNA methylation patterns. However, these approaches each have limitations.

Approaches based on somatic variant allele frequencies only work for patients that have known recurring cancer mutations, and reliable estimation requires that multiple mutations are present in the ctDNA. Since cfDNA targeted sequencing typically only covers a few hundred selected cancer genes because of the need for ultra-deep sequencing (˜10,000×), most patients will not have a sufficient number of detectable mutations to allow reliable tumor content estimation. ctDNA burden estimation based on SNVs may therefore be challenging when no clonal mutations exist among the targeted genes.

Alternatively, low-pass whole genome sequencing (Ip-WGS) yields segmental/arm-level CNAs, or epigenomics-associated fragmentation patterns that allow for inference of ctDNA burden. However, some cancers may not have sufficient levels of aneuploidy and chromosomal instability needed for robust estimation. Therefore, some cancers cannot be accurately monitored with this approach. Furthermore, low-pass whole genome sequencing approaches only work down to ˜3% tumor ctDNA fraction and the assay must be performed in addition to the standard targeted panel sequencing, wasting precious blood plasma.

Sequencing of DNA methylation patterns may provide a general approach to quantify the cellular origin of cfDNA. However, this technology is less efficient and more noisy (due to bisulfite conversion step) and is again not directly compatible with standard targeted panel sequencing, thereby wasting precious blood plasma.

Notably, both DNA methylation and Ip-WGS profiling require separate assays in addition to standard targeted gene sequencing, highlighting the need for approaches that simultaneously allow for profiling of actionable cancer mutations and quantitative estimation of ctDNA burden.

Thus, there is a need to provide an alternative method of estimating a disease burden, such as a ctDNA burden, and related kits and methods.

SUMMARY

In one aspect, there is provided a method of estimating a circulating tumor DNA (ctDNA) burden in a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cell-free DNA (cfDNA) that maps to one or more nucleosome-depleted region (NDR); and estimating the ctDNA burden based on said level of cfDNA, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood tissue and tumor tissue and/or (ii) is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject.

In one embodiment, determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR comprises: sequencing cfDNA fragments in the blood sample to obtain sequencing reads; and determining the number of sequencing reads that align with the one or more NDR to obtain said level of cfDNA that maps to one or more NDR.

In one embodiment, the method further comprises contacting the blood sample with one or more probe capable of binding to the one or more NDR to capture cfDNA fragments comprising the one or more NDR prior to the sequencing step.

In one embodiment, the NDR is selected from the group consisting of: a promoter region, a first exon-intron junction and combinations thereof.

In one embodiment, the estimated ctDNA burden positively correlates with a tumor burden in the subject.

In one embodiment, said transcript that is differentially expressed between healthy blood tissue and tumor tissue comprises a transcript which FPKM (Fragments Per Kilobase of transcript per Million) value differs by at least 10 times between healthy blood tissue and tumor tissue.

In one embodiment, said NDR that is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject comprises a NDR having different sequencing coverage in healthy blood tissue and in tumor tissue.

In one embodiment, said transcript that is differentially expressed in healthy blood tissue and tumor tissue is selected from the group consisting of: a transcript that is more highly expressed in healthy blood tissue than in tumor tissue, a transcript that is more highly expressed in tumor tissue than in healthy blood tissue and combinations thereof.

In one embodiment, said transcript which is differentially expressed between blood tissue and tumor tissue consists of transcript(s) that is more highly expressed in blood tissue than in tumor tissue.

In one embodiment, the one or more NDR comprises at least two NDRs, optionally six NDRs, further optionally ten NDRs.

In one embodiment, the total length of the one or more NDR is no more than 30 kb.

In one embodiment, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof.

In one embodiment, the method is a method of determining disease progression in a subject and the method further comprises: determining in a subsequent blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR; estimating the ctDNA burden based on said level of cfDNA; comparing the ctDNA burden estimated from said subsequent blood sample with the ctDNA burden estimated from said blood sample; and identifying the subject as having disease progression if the ctDNA burden estimated from said subsequent blood sample is higher than the ctDNA burden estimated from said blood sample and identifying otherwise if the ctDNA burden estimated from said subsequent blood sample is not higher than the ctDNA burden estimated from said blood sample.

In one embodiment, the method further comprises changing the treatment regimen received by the subject if the subject is identified as having disease progression.

In one embodiment, the tumor comprises colorectal tumor.

In one embodiment, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.

In one aspect, there is provided a kit for estimating a ctDNA burden in a subject, the kit comprising one or more probe that is capable of binding to one or more NDR, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood tissue and tumor tissue and/or (ii) is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject.

In one embodiment of the kit, said one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof.

In one embodiment of the kit, said tumor comprises colorectal tumor and said one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.

In one embodiment of the kit, the one or more probe comprises the sequence of one or more of SEQ ID NO: 1 to SEQ ID NO: 577, or a sequence sharing at least 75% sequence identity thereto.

Definitions

The term “treatment”, “treat” and “therapy”, and synonyms thereof as used herein refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) a medical condition, which includes but is not limited to diseases (such as cancer), symptoms and disorders. A medical condition also includes a body's response to a disease or disorder, e.g. inflammation. Those in need of such treatment include those already with a medical condition as well as those prone to getting the medical condition or those in whom a medical condition is to be prevented.

The term “subject” as used herein includes patients and non-patients. The term “patient” refers to individuals suffering or are likely to suffer from a medical condition such as cancer, while “non-patients” refer to individuals not suffering and are likely to not suffer from the medical condition. “Non-patients” include healthy individuals, non-diseased individuals and/or an individual free from the medical condition. The term “subject” includes humans and animals. Animals include murine and the like. “Murine” refers to any mammal from the family Muridae, such as mouse, rat, and the like.

The term “micro” as used herein is to be interpreted broadly to include dimensions from about 1 micron to about 1000 microns.

The term “nano” as used herein is to be interpreted broadly to include dimensions less than about 1000 nm.

The term “particle” as used herein broadly refers to a discrete entity or a discrete body. The particle described herein can include an organic, an inorganic or a biological particle. The particle used described herein may also be a macro-particle that is formed by an aggregate of a plurality of sub-particles or a fragment of a small object. The particle of the present disclosure may be spherical, substantially spherical, or non-spherical, such as irregularly shaped particles or ellipsoidally shaped particles. The term “size” when used to refer to the particle broadly refers to the largest dimension of the particle. For example, when the particle is substantially spherical, the term “size” can refer to the diameter of the particle; or when the particle is substantially non-spherical, the term “size” can refer to the largest length of the particle.

The terms “coupled” or “connected” as used in this description are intended to cover both directly connected or connected through one or more intermediate means, unless otherwise stated.

The term “associated with”, used herein when referring to two elements refers to a broad relationship between the two elements. The relationship includes, but is not limited to a physical, a chemical or a biological relationship. For example, when element A is associated with element B, elements A and B may be directly or indirectly attached to each other or element A may contain element B or vice versa.

The term “adjacent” used herein when referring to two elements refers to one element being in close proximity to another element and may be but is not limited to the elements contacting each other or may further include the elements being separated by one or more further elements disposed therebetween.

The term “and/or”, e.g., “X and/or Y” is understood to mean either “X and Y” or “X or Y” and should be taken to provide explicit support for both meanings or for either meaning.

Further, in the description herein, the word “substantially” whenever used is understood to include, but not restricted to, “entirely” or “completely” and the like. In addition, terms such as “comprising”, “comprise”, and the like whenever used, are intended to be non-restricting descriptive language in that they broadly include elements/components recited after such terms, in addition to other components not explicitly recited. For example, when “comprising” is used, reference to a “one” feature is also intended to be a reference to “at least one” of that feature. Terms such as “consisting”, “consist”, and the like, may in the appropriate context, be considered as a subset of terms such as “comprising”, “comprise”, and the like. Therefore, in embodiments disclosed herein using the terms such as “comprising”, “comprise”, and the like, it will be appreciated that these embodiments provide teaching for corresponding embodiments using terms such as “consisting”, “consist”, and the like. Further, terms such as “about”, “approximately” and the like whenever used, typically means a reasonable variation, for example a variation of +/−5% of the disclosed value, or a variance of 4% of the disclosed value, or a variance of 3% of the disclosed value, a variance of 2% of the disclosed value or a variance of 1% of the disclosed value.

Furthermore, in the description herein, certain values may be disclosed in a range. The values showing the end points of a range are intended to illustrate a preferred range. Whenever a range has been described, it is intended that the range covers and teaches all possible sub-ranges as well as individual numerical values within that range. That is, the end points of a range should not be interpreted as inflexible limitations. For example, a description of a range of 1% to 5% is intended to have specifically disclosed sub-ranges 1% to 2%, 1% to 3%, 1% to 4%, 2% to 3% etc., as well as individually, values within that range such as 1%, 2%, 3%, 4% and 5%. It is to be appreciated that the individual numerical values within the range also include integers, fractions and decimals. Furthermore, whenever a range has been described, it is also intended that the range covers and teaches values of up to 2 additional decimal places or significant figures (where appropriate) from the shown numerical end points. For example, a description of a range of 1% to 5% is intended to have specifically disclosed the ranges 1.00% to 5.00% and also 1.0% to 5.0% and all their intermediate values (such as 1.01%, 1.02% . . . 4.98%, 4.99%, 5.00% and 1.1%, 1.2% . . . 4.8%, 4.9%, 5.0% etc.,) spanning the ranges. The intention of the above specific disclosure is applicable to any depth/breadth of a range.

Additionally, when describing some embodiments, the disclosure may have disclosed a method and/or process as a particular sequence of steps. However, unless otherwise required, it will be appreciated that the method or process should not be limited to the particular sequence of steps disclosed. Other sequences of steps may be possible. The particular order of the steps disclosed herein should not be construed as undue limitations. Unless otherwise required, a method and/or process disclosed herein should not be limited to the steps being carried out in the order written. The sequence of steps may be varied and still remain within the scope of the disclosure.

Furthermore, it will be appreciated that while the present disclosure provides embodiments having one or more of the features/characteristics discussed herein, one or more of these features/characteristics may also be disclaimed in other alternative embodiments and the present disclosure provides support for such disclaimers and these associated alternative embodiments.

DESCRIPTION OF EMBODIMENTS

Exemplary, non-limiting embodiments of a method of estimating a disease burden, such as a ctDNA burden, in a subject and related kits and methods are disclosed hereinafter.

In various embodiments, there is provided a method of estimating, predicting and/or determining one or more of: a disease burden, a cancer burden, a tumor burden, a circulating tumor DNA (ctDNA) burden, a level of ctDNA, an amount of ctDNA, a proportion of ctDNA, a fraction of ctDNA and a ctDNA content in a subject. In various embodiments, the method comprises determining in a sample obtained from the subject, a level, an amount, a proportion, a fraction and/or a content of DNA, optionally cell-free DNA (cfDNA), that aligns with, belongs to, maps to, corresponds to, is similar to and/or identical to at least one genomic region, and estimating, predicting and/or determining one or more of: the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, the amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content in the subject based on the level, the amount, the proportion, the fraction and/or the content of DNA. In some embodiments, the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, the amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content comprises the absolute disease burden, cancer burden, tumor burden, ctDNA burden, level of ctDNA, amount of ctDNA, proportion of ctDNA, fraction of ctDNA and/or ctDNA content.

The estimation, prediction and/or determination may be quantitative, semi-quantitative or qualitative. In various embodiments, the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, the amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content is associated with or correlates with the level, the amount, the proportion, the fraction and/or the content of DNA, optionally cfDNA, in the subject.

In various embodiments, the at least one genomic region comprises a gene. In various embodiments, the at least one genomic region comprises a coding region. In various embodiments, the at least one genomic region comprises a non-coding region (e.g. a region that is far away from genes, a regulatory region such as enhancer etc.). In various embodiments, the at least one genomic region comprises a nucleosome-depleted region (NDR). In various embodiments, the nucleosome-depleted region comprises a gene. In various embodiments, the nucleosome-depleted region comprises a coding region. In various embodiments, the nucleosome-depleted region comprises a non-coding region.

In various embodiments, the at least one genomic region comprises at least one coding region/gene and at least one non-coding region. In various embodiments, determining in the sample a level (or an amount, a proportion, a fraction and/or a content) of DNA that maps to (or aligns with, corresponds to, belongs to, is similar to and/or is identical to) at least one genomic region comprises determining a level of DNA that maps to each of a plurality of genomic regions, the plurality of genomic regions comprising a greater number/proportion of coding region(s)/gene(s) than non-coding region(s). In other words, in various embodiments, the non-coding regions make up a small/minority set of the plurality of regions that are being mapped to.

A NDR may be a region that has a relatively low nucleosome occupancy level. For example, a promoter region upstream of a transcriptional start site (TSS) often displays low nucleosome occupancy level for a typical gene. For example, regulatory regions tend to be nucleosome depleted. In various embodiments, the at least one NDR comprises a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction. An intron-exon junction may be a first intron-exon junction, a second intron-exon junction, a third intron-exon junction, a fourth intron-exon junction etc. An exon-intron junction may be a first exon-intron junction, a second exon-intron junction, a third exon-intron junction, a fourth exon-intron junction etc. In various embodiments, the NDR is selected from the group consisting of: a promoter region, a first exon-intron junction and combinations thereof. In various examples, cfDNA coverage/degradation pattern at a first exon-intron junction and/or a promoter region is found to possess the capability or better capability to infer gene expression and/or predict ctDNA burden.

In various embodiments, the NDR comprises the NDR of a gene which is differentially expressed in healthy blood tissue/cell and diseased tissue/cell. In various embodiments, the NDR comprises the NDR of a gene which transcript is differentially expressed in healthy blood tissue/cell and diseased tissue/cell. Because a gene usually comprises multiple alternative transcripts with different genomic positions, determining the gene expression at the transcript level (as compared to at the gene level) may allow for a more precise mapping of the NDR e.g. the promoter and junction locations. A gene which transcript is differentially expressed in healthy blood tissue/cell and diseased tissue/cell may be identified by RNA sequencing or any other suitable methods known in the art. A gene which transcript is differentially expressed in healthy blood tissue/cell and diseased tissue/cell may also be identified by analysing transcript expression data available at public databases e.g. the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA) program etc. A transcript which is differentially expressed in healthy blood tissue/cell and diseased tissue/cell may have different FPKM (fragments per kilobase of transcript per million mapped fragments/reads) or RPKM (Reads Per Kilobase of transcript, per Million mapped reads), or TPM (Transcripts Per Million) values in healthy blood tissue/cell and in diseased tissue/cell (e.g. as determined by sequencing).

In various embodiments, the difference in the expression or FPKM/RPKM/TPM value of the transcript in healthy blood tissue/cell and in diseased tissue/cell is at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or at least about 100%. In various embodiments, the difference in the expression of the transcript FPKM/RPKM/TPM value in healthy blood tissue/cell and in diseased tissue/cell is at least about 0.1 fold, at least about 0.2 fold, at least about 0.3 fold, at least about 0.4 fold, at least about 0.5 fold, at least about 0.6 fold, at least about 0.7 fold, at least about 0.8 fold, at least about 0.9 fold, at least about 1 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 11 fold, at least about 12 fold, at least about 13 fold, at least about 14 fold or at least about 15 fold. In various embodiments, the difference in the expression of the transcript FPKM/RPKM/TPM value in healthy blood tissue/cell and in diseased tissue/cell is at least about 0.1 times, at least about 0.2 times, at least about 0.3 times, at least about 0.4 times, at least about 0.5 times, at least about 0.6 times, at least about 0.7 times, at least about 0.8 times, at least about 0.9 times, at least about 1 times, at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 11 times, at least about 12 times, at least about 13 times, at least about 14 times or at least about 15 times. In various embodiments, the FPKM/RPKM/TPM value comprises a median FPKM/RPKM/TPM value obtained from a plurality of healthy blood tissue/cell samples and/or a plurality of diseased tissue/cell samples.

In various embodiments, the NDR is degraded to different extents in healthy blood tissue/cell and in blood tissue/cell of a diseased subject. In various embodiments, the NDR has different degradation patterns/signals in healthy blood tissue/cell and in blood tissue/cell of a diseased subject. For example, when sequencing cfDNA in a healthy blood tissue/cell sample and in blood tissue/cell sample of a diseased subject, a greater or smaller number/amount (i.e. a substantially different or non-identical number/amount) of fragments/reads may map to the NDR in the healthy blood tissue/cell sample as compared to the blood tissue/cell sample of the diseased subject. For example, when sequencing cfDNA in a healthy blood tissue/cell sample and in a blood tissue/cell sample of a diseased subject, the read depth or coverage of the NDR may be higher or lower in the healthy blood tissue/cell sample as compared to the blood tissue/cell sample of a diseased subject. In various embodiments therefore, the NDR has different (or non-similar or non-identical) read depth or coverage in healthy blood tissue/cell and in blood tissue/cell of a diseased subject.

The read depth or coverage of a NDR may comprise a relative read depth or relative coverage of the NDR. A relative read depth or relative coverage of a NDR may be obtained, for example, by normalizing/dividing the raw read depth/coverage across the NDR (or optionally a mean raw read depth/coverage across the NDR for multiple samples/runs) by a normalization factor. In one example, the normalization factor comprises the read depth or coverage (or optionally a mean read depth/coverage for multiple samples/runs) of region(s) flanking the NDR e.g. the flanking upstream and/or downstream regions. In one example, the normalization factor is the mean coverage of the upstream and downstream flanks of the NDR. In one example therefore, the relative read depth or relative coverage of a NDR is the mean raw read depth/coverage across the NDR divided by the mean raw read depth/coverage of the upstream and downstream flanks.

In some embodiments, the flanking region(s) is immediately upstream or downstream of the NDR, or contiguous with the NDR. In some embodiments, the flanking region(s) is separated from the NDR by one or more nucleotides/bases. In various embodiments, the flanking region(s) is no more than about 5000 base pairs (bp), no more than about 4500 bp, no more than about 4000 bp, no more than about 3500 bp, no more than about 3000 bp, no more than about 2500 bp or no more than about 2000 bp from the NDR or an end of the NDR. In various embodiments, the flanking region(s) is at least about 50 bp, at least about 100 bp, at least about 150 bp, at least about 200 bp, at least about 250 bp, at least about 300 bp, at least about 350 bp, at least about 400 bp, at least about 450 bp, at least about 500 bp, at least about 550 bp, at least about 600 bp, at least about 650 bp, at least about 700 bp, at least about 750 bp, at least about 800 bp, at least about 850 bp, at least about 900 bp, at least about 950 bp, or least about 1000 bp from the NDR or an end of the NDR.

In various embodiments, the size/length of flanking region(s) is at least about 50 bp, at least about 100 bp, at least about 150 bp, at least about 200 bp, at least about 250 bp, at least about 300 bp, at least about 350 bp, at least about 400 bp, at least about 450 bp, at least about 500 bp, at least about 550 bp, at least about 600 bp, at least about 650 bp, at least about 700 bp, at least about 750 bp, at least about 800 bp, at least about 850 bp, at least about 900 bp, at least about 950 bp, or least about 1000 bp.

In one example, the NDR is about −300 bp to about 300 bp, about −200 bp to about 100 bp or about −150 bp to about 50 bp relative to a transcription start site (TSS) and the normalization factor is the mean coverage of an upstream flank that is about −2000 bp to about −1000 bp relative to the TSS and a downstream flank that is about 1000 bp to about 2000 bp relative to the TSS.

In various embodiments, a NDR that is degraded to different extents in healthy blood tissue/cell and in blood tissue/cell of a diseased subject may be identified by comparing the relative depth/coverage of the NDR in healthy blood tissue/cell and in the blood tissue/cell of a diseased subject. For example, if the relative depth/coverage of the NDR in healthy blood tissue/cell and in the blood tissue/cell of a diseased subject are different, the NDR is considered to a NDR that is degraded to different extents in healthy blood tissue/cell and in blood tissue/cell of a diseased subject. In various embodiments, determining the relative depth/coverage of a NDR in healthy blood tissue/cell and/or in blood tissue/cell of a diseased subject comprises determining the coverage of each position in an about 8 k-bp window, about 6 k-bp window, about 4 k-bp window, about 2 k-bp window or about 1 k-bp window spanning from about −4000 to +4000 bp, from about −3000 to +3000 bp, from about −2000 to +2000 bp, from about −1000 to +1000 bp or from about −500 to +500 bp with respect the NDR (e.g. end(s) of the NDR); and optionally normalizing the coverage by the mean coverage of the upstream region (e.g. −8000 to −4000 bp, −4000 to −2000 bp, −3000 to −1000 bp, −2000 to −1000 bp or −1000 to −500 bp with respect to the NDR (e.g. end(s) of the NDR)) and/or downstream region (e.g. +4000 bp to +8000 bp, +2000 to +4000 bp, +1000 to +3000 bp+1000 to +2000 bp or +500 to +1000 bp with respect to the NDR (e.g. end(s) of the NDR) to obtain a relative depth/coverage for the NDR. In some examples, the coverage of each position in a region located downstream of a NDR (e.g. a promoter) is determined. In some examples, the coverage of each position in a region located from about −350 bp to about −50 bp or from about −300 to about −100 bp with respect a NDR (e.g. an end of a first exon) is determined.

In various embodiments, the difference in read depth or coverage (or relative read depth or coverage) in healthy blood tissue/cell and in blood tissue/cell of a diseased subject is measured by computing a coverage score (or relative coverage score). In various embodiments, the coverage score (or relative coverage score) is computed by the following formula:

${score} = \frac{{{mean}({diseased})} - {{mean}({healthy})}}{\sqrt{s.d.({diseased})}}$

where mean(diseased) and mean(healthy) are the mean of average coverages (or relative coverages) at NDRs across diseased blood tissue/cell (e.g. plasma samples of diseased subjects) and healthy blood tissue/cell (e.g. healthy plasma samples) respectively, and s.d. (diseased) is the standard deviation of average coverages (or relative coverages) at NDRs across diseased blood tissue/cell.

In various embodiments, the coverage values negatively correlate with expression level. In some examples therefore, blood genes/transcripts (e.g. genes/transcripts show a higher FPKM value in normal blood than in tumor) have a higher coverage in diseased samples than in healthy samples. Thus, the blood genes/transcripts have a positive value of relative coverage score, as mean(diseased)>mean(healthy). In some examples, tumor genes/transcripts (e.g. genes/transcripts show a higher FPKM value in tumor than in normal blood) have a lower coverage in disease samples than in healthy samples. Thus, the tumor genes have a negative value of relative coverage score, as mean(diseased)<mean(healthy).

In various embodiments, the NDR has a coverage score or relative coverage score of less than about 0 and/or more than about 0. In various embodiments, the NDR has a coverage score or relative coverage score of less than about −0.1, less than about −0.2, less than about −0.3, less than about −0.4, less than about −0.5, less than about −0.6, less than about −0.7, less than about −0.8, less than about −0.9 or less than about −1.0. In various embodiments, the NDR has a coverage score or relative coverage score of more than about 0.1, more than about 0.2, more than about 0.3, more than about 0.4, more than about 0.5, more than about 0.6, more than about 0.7, more than about 0.8, more than about 0.9 or more than about 1.0.

As used herein, “blood”, “blood tissue” or “blood sample” refers to whole blood or fractions thereof, such as a plasma fraction or a serum fraction. As used herein “healthy blood”, “healthy blood tissue” or “healthy blood sample” refers to the whole blood or fractions thereof of a healthy subject, or a subject who does not suffer from the disease. Conversely, “diseased blood”, “diseased blood tissue” or “diseased blood sample” as used herein refers to the whole blood or fractions thereof of a diseased subject, or a subject who suffers from the disease. In various embodiments, “diseased blood”, “diseased blood tissue” or “diseased blood sample” does not indicate that a disease necessarily resides in the blood per se. For example, “diseased blood”, “diseased blood tissue” or “diseased blood sample” may refer to the blood, tissue or sample of a subject suffering from colorectal cancer and having no blood diseases, and “healthy blood”, “healthy blood tissue” or “healthy blood sample” may refer to the blood, tissue or sample of a subject who does not suffer from colorectal cancer.

In various embodiments, the sample obtained from the subject comprises a liquid sample. In various embodiments, the sample comprises a biological fluid sample. In various embodiments, the liquid/biological fluid sample comprises one or more of blood, serum, plasma, sputum, lavage fluid, cerebrospinal fluid, interstitial fluid, urine, feces, milk, semen, sweat, tears, saliva, and the like. In various embodiments, the sample comprises a blood sample (e.g. whole blood sample or processed fractions thereof). In various embodiments, the sample comprises a plasma sample. In various embodiments, the sample comprises cfDNA. In various embodiments, the sample comprises cfDNA, for example, cfDNA extracted/isolated/purified from a blood sample obtained from the subject.

In various embodiments, the disease comprises a proliferative disease and the diseased tissue/cell comprises a proliferative tissue/cell. In various embodiments, the disease comprises a malignant disease and the diseased tissue/cell comprises a malignant tissue/cell. In various embodiments, the malignant disease comprises cancer and the diseased tissue/cell comprises a cancer tissue/cell. In various embodiments, the cancer comprises solid tumor cancers.

In various embodiments therefore, there is provided a method of estimating a ctDNA burden in a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more nucleosome-depleted region (NDR); and estimating the ctDNA burden based on said level of cfDNA, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood tissue and tumor tissue and/or (ii) is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject. Advantageously, a level of cfDNA that maps to selected NDR(s) is identified to be a good estimator of or proxy for tumor burden or ctDNA burden.

In various embodiments, the estimated ctDNA burden associates/correlates, optionally positively associates/correlates with a tumor burden in the subject. In various embodiments, the higher the estimated ctDNA burden in the subject, the higher the tumor burden in the subject. In various embodiments, the higher the estimated ctDNA burden in the subject, the higher the estimated amount of cancer/tumor cells in the subject. In various embodiments, the higher the estimated ctDNA burden in the subject, the higher the estimated mass/size/volume of tumor in the subject. In various embodiments, the association/correlation, optionally positive association/correlation, may be linear (i.e. the ratio of change is constant) or non-linear (i.e. the ratio of change is not constant).

In various embodiments, the estimated ctDNA burden is associated/correlated with the level of cfDNA that maps to one or more NDRs. The association/correlation may be positive and/or negative, linear and/or non-linear and monotonic and/or non-monotonic. For example, the estimated ctDNA burden may be positively associated/correlated with the level of cfDNA that maps to a first NDR and negatively associated/correlated with the level of cfDNA burden that maps to a second NDR. For example, the estimated ctDNA burden may be linearly associated/correlated (e.g. positive or negative) with the level of cfDNA that maps to a first NDR and non-linearly associated/correlated with the level of cfDNA burden that maps to a second NDR. For example, the estimated ctDNA burden may be monotonically associated/correlated with the level of cfDNA that maps to a first NDR and non-monotonically associated/correlated with the level of cfDNA that maps to a second NDR.

In one example, the signs of the coefficients for the one or more NDRs in a trained model correspond to the sign of the differential expression of the associated transcripts in tumor tissue relative to healthy blood tissue. In various embodiments, an NDR associated with a cancer-specific gene/transcript or a tumor gene/transcript (e.g. a gene/transcript that shows a higher FPKM value in tumor than in normal blood) has a negative coefficient/correlation with the estimated ctDNA burden. In various embodiments, an NDR associated with a blood gene/transcript (e.g. a gene/transcript that shows a higher FPKM value in normal blood than in tumor) has a positive coefficient/correlation with the estimated ctDNA burden. In various embodiments, the estimated ctDNA burden is negatively associated/correlated with a level of cfDNA that maps to one or more NDR of a gene which transcript is more highly expressed in tumor tissue than in healthy blood tissue and/or the estimated ctDNA burden is positively associated/correlated with a level of cfDNA that maps to one or more NDR of a gene which transcript is more highly expressed in healthy blood tissue than in tumor tissue. In some embodiments, the estimated ctDNA burden is linearly correlated with the level of cfDNA that maps to one or more NDRs.

In various embodiments, the determining step comprises sequencing the DNA or cfDNA present in the blood sample obtained from the subject. Examples of sequencing techniques include next-generation sequencing, amplicon-based sequencing, paired-end sequencing, Sanger sequencing etc. In some embodiments, sequencing the DNA or cfDNA present in the blood sample comprises subjecting the DNA or cfDNA present in the blood sample to deep sequencing. In one embodiment, sequencing the DNA or cfDNA present in the blood sample comprises subjecting the DNA or cfDNA present in the blood sample to next-generation sequencing. In some examples, deep sequencing is performed such that the depth/coverage at the one or more NDR/at least one NDR is at least about 10×, at least about 25×, at least about 50×, at least about 100×, at least about 200×, at least about 300×, at least about 400×, at least about 500×, at least about 600×, at least about 700×, at least about 800×, at least about 900× or at least about 1000×, at least about 2000×, at least about 3000×, at least about 4000×, at least about 5000× or at least about 6000×. In various embodiments, the sequencing does not comprise ultra-deep sequencing. In various embodiments, the depth/coverage at the one or more NDR/at least one NDR is or is kept to less than about 10,000×, less than about 9000×, less than about 8000×, less than about 7000×, less than about 6000×, less than about 5000×, less than about 4000×, less than about 3000×, less than about 2000× or less than about 1000×. In various embodiments, the depth/coverage at the one or more NDR/at least one NDR is or is kept to no more than about 10,000×, no more than about 9000×, no more than about 8000×, no more than about 7000×, no more than about 6000×, no more than about 5000×, no more than about 4000×, no more than about 3000×, no more than about 2000× or no more than about 1000×.

In various embodiments, determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR comprises sequencing cfDNA/cfDNA fragments in the blood sample to obtain sequencing reads; and determining the number of sequencing reads that align with the one or more NDR to obtain said level of cfDNA that maps to one or more NDR. In various embodiments, determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR comprises sequencing any cfDNA/cfDNA fragments present in the blood sample and determining the depth/read depth/coverage/sequencing coverage at the one or more NDR. The depth/read depth/coverage may be a relative depth/read depth/coverage/sequencing coverage. For example, the depth/read depth/coverage/sequencing coverage may be normalized/divided by a normalization factor, for example, a normalization factor as described herein, to obtain the relative depth/read depth/coverage/sequencing coverage. In one example, the relative depth/read depth/coverage/sequencing coverage is obtained by dividing/normalizing the depth/read depth/coverage/sequencing coverage (or mean depth/read depth/coverage/sequencing coverage) across the one or more NDR by the depth/read depth/coverage/sequencing coverage (or mean depth/read depth/coverage/sequencing coverage) of an upstream flank and/or a downstream flank, for example, an upstream flanking region and/or a downstream flanking region as described herein. In some embodiments therefore, the method further comprises determining the number of sequencing reads that align with one or more regions flanking the one of more NDR. In some embodiments, the method further comprises determining the depth/read depth/coverage/sequencing coverage at the one or more region flanking the one of more NDR.

The sequencing may be targeted or untargeted. Where the sequencing comprises targeted sequencing, probe(s) may be used to capture and isolate specific genomic regions for sequencing. In some embodiments therefore, the method further comprises contacting the blood sample with one or more probe capable of binding to the one or more NDR to capture cfDNA/cfDNA fragments comprising the one or more NDR prior to the sequencing step.

In various embodiments, determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR comprises performing quantitative polymerase chain reaction (qPCR) or real-time polymerase chain reaction (real-time PCR) to determine the amount/proportion of cfDNA that maps to one or more NDR. In various embodiments, the performing step comprises contacting the sample with a primer that is capable of hybridizing/binding (e.g. under stringent conditions) to or a primer that is specific to the one or more NDR.

In various embodiments, the method further comprises amplifying the cfDNA in the blood sample. The amplification step may be carried out before the step of determining a level of cfDNA. The amplification step may also be carried out before the step of sequencing cfDNA/cfDNA fragments in the blood sample and/or before the step of contacting the blood sample with the one or more probe. Amplification reactions known in the art may be employed. The amplification reactions may include but are not limited to polymerase chain reaction (PCR), ligase chain reaction (LCR), loop mediated isothermal amplification (LAMP), nucleic acid sequence based amplification (NASBA), self-sustained sequence replication (3SR), rolling circle amplification (RCA) or any other process whereby one or more copies of a particular polynucleotide sequence or nucleic acid sequence may be generated from a polynucleotide template sequence or nucleic acid template sequence.

In various embodiments, the method further comprises processing the cfDNA and/or its associated data. In various embodiments, the cfDNA are trimmed at one or both ends to retain only a central region and/or data associated with a central region of the cfDNA. Advantageously, trimming the cfDNA and/or its associated data from one or both ends to retain only a central region and/or data associated with a central region of the cfDNA may amplify a degradation signal and/or increases a coverage signal. In various embodiments, the trimmed cfDNA/central region is no more than about 70 bp, no more than about 60 bp or no more than about 50 bp in length. In various embodiments, the trimmed cfDNA/central region is about 70 bp, about 60 bp or about 50 bp in length. In one embodiment, the central region is about 61 bp. The method may also work with an untrimmed cfDNA (e.g. a cfDNA of about 151 bp), although the signal produced may be weaker.

In various embodiments, the cfDNA and/or its associated data are trimmed in-silico e.g. by use of the software BamUtil. In various embodiments, the cfDNA and/or its associated data are trimmed after sequencing.

In various embodiments, said NDR that is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject comprises a NDR having different depth/read depth/coverage/sequencing coverage in healthy blood tissue and in tumor tissue.

In various embodiments, said transcript that is differentially expressed between healthy blood tissue and tumor tissue comprises a transcript which FPKM value differs by at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times or at least about 10 times between healthy blood tissue and tumor tissue (e.g. as determined by sequencing).

In various embodiments, said transcript that is differentially expressed between healthy blood tissue and tumor tissue comprises a transcript which FPKM value in healthy blood tissue is less than about 30, less than about 20, less than about 10, less than about 5, less than about 3, less than about 1, less than about 0.5, less than about 0.1, less than about 0.05 or less than about 0.01. In one embodiment, the FPKM value of the transcript in healthy blood tissue in less than about 1. In various embodiments, the FPKM value of the transcript in healthy blood tissue is more than about 0.01, more than about 0.05, more than about 0.1, more than about 0.5, more than about 1, more than about 3, more than about 5, more than about 10, more than about 20 or more than about 30. In one embodiment, the FPKM value of the transcript in healthy blood tissue is more than about 10. In various embodiments, the FPKM value of the transcript in healthy blood tissue is between about 0.01 and about 0.1, between about 0.1 and about 1, between about 1 and about 5 or between about 5 and about 30.

In various embodiments, said transcript that is differentially expressed between healthy blood tissue and tumor tissue comprises a transcript which FPKM value in tumor tissue is less than about 30, less than about 20, less than about 10, less than about 5, less than about 3, less than about 1, less than about 0.5, less than about 0.1, less than about 0.05 or less than about 0.01. In one embodiment, the FPKM value of the transcript in tumor tissue in less than about 1. In various embodiments, the FPKM value of the transcript in tumor tissue is more than about 0.01, more than about 0.05, more than about 0.1, more than about 0.5, more than about 1, more than about 3, more than about 5, more than about 10, more than about 20 or more than about 30. In one embodiment, the FPKM value of the transcript in tumor tissue is more than about 10. In various embodiments, the FPKM value of the transcript in tumor tissue is between about 0.01 and about 0.1, between about 0.1 and about 1, between about 1 and about 5 or between about 5 and about 30.

Some transcripts may be more highly expressed in healthy blood tissue than tumor tissue. In various embodiments, a blood transcript comprises a transcript that is more highly expressed in healthy blood tissue than tumor tissue. Some transcripts may be more highly expressed in tumor tissue than blood tissue. In various embodiments, a tumor transcript comprises a transcript that is more highly expressed in tumor tissue than blood tissue. The one or more NDR may comprise at least about 10%, at least about 20%, or at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or about 100% NDRs which transcripts more highly expressed in healthy blood tissue than tumor tissue. The one or more NDR may comprise at least about 10%, at least about 20%, or at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or at about 100% NDRs which transcripts more highly expressed in tumor tissue than in blood tissue. The one or more NDR may comprise at least about one, at least about two or at least about three NDRs which transcripts more highly expressed in healthy blood tissue than tumor tissue and/or at least about one, at least about two or at least about three NDRs which transcripts are more highly expressed in tumor tissue than in blood tissue.

In various embodiments, said transcript which is differentially expressed in healthy blood tissue and tumor tissue is selected from the group consisting of: a transcript that is more highly expressed in healthy blood tissue than tumor tissue, a transcript that is more highly expressed in tumor tissue than healthy blood tissue and combinations thereof. In one embodiment, said transcript which is differentially expressed between blood tissue and tumor tissue consists of transcript(s) that is more highly expressed in tumor tissue than blood tissue. In one embodiment, said transcript which is differentially expressed between blood tissue and tumor tissue consists of transcript(s) that is more highly expressed in blood tissue than tumor tissue. In one embodiment, said transcript does not comprise a transcript which is more highly expressed in tumor tissue than blood tissue. Without being bound by theory, it is believed that tumor-derived DNA component in cancer plasma weakens the blood-specific DNA degradation pattern, and thus the decay of blood-specific signal (alone i.e. without determining the signal of any tumor-associated genes) may be used to robustly estimate a ctDNA content, regardless of cancer types.

In various embodiments therefore, the method is suitable for estimating a disease burden for a specific cancer type, a specific group of cancers, or for all cancers in general (i.e. pan-cancer). In various embodiments, the method comprises a method of estimating a ctDNA burden or tumor burden associated with one or more of the following cancers: bladder cancer, bladder urothelial carcinoma, breast cancer, breast invasive carcinoma, cervical cancer, cervical squamous cell carcinoma, endocervical adenocarcinoma, colorectal cancer, esophageal cancer, esophageal carcinoma, brain cancer, glioblastoma multiforme, head and neck cancer, head and neck squamous cell carcinoma, kidney cancer, renal cell cancer, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver cancer, liver hepatocellular carcinoma, lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, ovarian cancer, ovarian serous cystadenocarcinoma, pancreatic cancer, pancreatic adenocarcinoma, prostate cancer, prostate adenocarcinoma, skin cancer, skin cutaneous melanoma, gastric cancer, stomach cancer, stomach adenocarcinoma, thyroid cancer, thyroid carcinoma, endometrial cancer, uterine cancer, uterine corpus endometrial carcinoma, reproductive cancers, gastrointestinal cancers, respiratory cancers, or subtypes thereof. Thus, in various embodiments, the subject has or suffers from one or more of these cancers. In various embodiments, the tumor-bearing subject bears one or more of these tumors. In various embodiments, the subject or tumor-bearing subject does not have or does not suffer from blood cancer/hematologic cancer/hematologic malignancy.

In one embodiment, the method comprises a method of estimating a tumor burden associated with colorectal cancer. In one embodiment, the subject has or suffers from colorectal cancer. In one embodiment, the tumor-bearing subject bears a colorectal tumor. In one embodiment, the method comprises a method of estimating a ctDNA burden or tumor burden associated with breast cancer. In one embodiment, the subject has or suffers from breast cancer. In one embodiment, the tumor-bearing subject bears a breast tumor.

In one embodiment, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with a specific cancer type or a specific group of cancers, the NDR comprises at least one NDR of a gene which transcript shows a higher FPKM value in tumor belonging to the specific cancer type or the specific group of cancers than in healthy/normal blood. In some examples, the transcript has a FPKM_(tumor)>about 5 or >about 10 and a FPKM_(blood)<about 1. In one embodiment, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with any cancer in general (e.g. pan-cancer), the NDR comprises at least one NDR of a gene which transcript shows a higher FPKM value in normal blood than in tumor. In some examples, the transcript has a FPKM_(blood)>about 5 or >about 10 and a FPKM_(tumor)<about 1. In various embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with any cancer in general (e.g. pan-cancer), the NDR consists of NDR(s) of gene(s) which transcript(s) shows a higher FPKM value in normal blood than in tumor.

In various embodiments, the one or more NDR comprises at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, at least about ten, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19 or at least about 20 NDRs. In various embodiments, the one or more NDR comprises the NDR of at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, at least about ten genes, at least about 11, at least about 12, at least about 13, at least about 14, at least about 15, at least about 16, at least about 17, at least about 18, at least about 19 or at least about 20 genes or distinct genes.

In some embodiments, the one or more NDR comprises at least about two NDRs, optionally about six NDRs, further optionally about ten NDRs. In some embodiments, the one or more NDR comprises the NDR of at least about two genes (or distinct genes), optionally about six genes (or distinct genes), further optionally about ten genes (or distinct genes). In some embodiments, the one or more NDR comprises at least about four NDRs or the NDRs of at least about four genes or distinct genes. In some embodiments, the one or more NDR comprises no more than about nine NDRs or NDRs of no more than about nine genes or distinct genes. In some embodiments, the one or more NDR comprises about four to about nine NDRs or NDRs of about four to about nine genes or distinct genes. In some embodiments, the one or more NDR comprises about six NDRs or NDRs of about six genes or distinct genes. In some embodiments, the one or more NDR comprises no more than about 13 NDRs or NDRs of no more than about 13 genes or distinct genes. In some embodiments, the one or more NDR comprises about nine, about 10, about 11, about 12 or about 13 NDRs or NDRs of about nine, about 10, about 11, about 12 or about 13 genes or distinct genes. The suitable number of NDRs, genes or features may be further varied, and is within the purview of a person skilled in the art. The number or the reasonable range of numbers of NDRs, genes or features may be determined, for example, by checking an error evolution with the number of top predictive genes or features (e.g. genes or features that are selected most frequently as being predictive by a machine learning model in multiple iterations).

In various embodiments, the NDRs/genes comprises one or more NDRs/genes listed in one or more of Table 1, Table 2, Table S3, Table S10, Table S14, Table S15, Table S16, Table S17, Table S18, Table S19, Table S20 and Table S21.

In various embodiments, the NDRs/genes comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ABHD5, ABTB1, ACAP1, AC01, ACRBP, ACSL1, ADAM8, ADIRF, AGR2, AGR3, AHSP, AK2, AKNA, ALAS2, ALDH18A1, ALOX5, ANKS4B, ANPEP, AOAH, APOBEC3A, ARAP1, ARHGAP25, ARHGAP26, ARHGAP30, ARHGAP9, ARHGEF16, ARHGEF35, ARIDSA, ARRB2, ARSE, ATG16L2, ATP2A2, ATP2C2, ATP5G1, ATP5G3, ATP6V1B2, AXIN2, AZGP1, AZU1, B3GNT3, BATF2, BCAR1, BCL2L15, BCL2L2, BCL6, BDH1, BDH2, BEST1, BGN, BIN2, BIRCS, BMP4, BMX, BOK, BPI, BSPRY, BTK, BTNL8, C10orf54, C11orf21, C16orf54, C19orf33, C19orf35, C1orf162, C1orf210, C1orf228, C1QTNF5, C3, C5AR2, C6orf203, C6orf25, C8orf59, CA1, CA4, CALD1, CAMP, CAPNS, CARS2, CCDC88B, CCL20, CCM2, CCND3, CCR7, CD177, CD244, CD276, CD300E, CD300LB, CD300LF, CD37, CD44, CD53, CD55, CDC42SE1, CDCP1, CDH1, CDH17, CDHRS, CDK4, CDK5RAP2, CDX1, CEACAM1, CEACAM3, CEACAM4, CEACAM5, CELF2, CENPF, CFD, CFP, CFTR, CHCHD6, CHID1, CKB, CKMT1B, CLC, CLDN7, CLEC12A, CLEC4D, CLEC4E, CMTM2, CNN2, CORO1A, CORO7, COTL1, COX6C, CR1, CRB3, CSF3R, CTGF, CTNND1, CXCR1, CXCR2, CYBA, CYTH4, DDC, DDR1, DDX10, DEF8, DEFA1, DEFA1B, DEFA3, DEFA4, DENND1C, DENND3, DHRS13, DHX34, DMTN, DNAH17, DOCK2, DOK3, DPEP2, DYSF, ECE1, ECT2, EEF1E1, EFNA3, EGLN2, E124, ELANE, ELF3, EMP1, ENTPD2, ENTPD6, EPB42, EPCAM, EPHA2, EPS8L3, ERBB2, ERBB3, EVI2B, F3, FAM101A, FAM109A, FAM212B, FAM213B, FAM49B, FAM60A, FAM65B, FAM83E, FAM84A, FBL, FBXL5, FCAR, FCGR2A, FCGR3B, FCN1, FERMT1, FERMT3, FES, FFAR2, FGD3, FGFR4, FGFRL1, FGR, FKBP8, FLOT2, FMNL1, FN1, FOLR3, FOXA2, FPR1, FPR2, FUT2, FUT6, FUT7, GATA1, GBP3, GCA, GGT6, GJB2, GLRX3, GLT1D1, GMFG, GMNN, GNG2, GNLY, GOLT1A, GP9, GPC4, GPR35, GPRCSA, GPSM3, GPX2, GRAMD1A, GRAP2, GRTP1, GZMH, H2AFY2, HBA1, HBA2, HBB, HBD, HBG1, HBG2, HBM, HBQ1, HCK, HCLS1, HID1, HK3, HKDC1, HMBS, HMGB3, HMGCS2, HN1L, HNF4A, HTRA1, ICAM3, IFI30, IFITM1, IFITM2, IFT172, IKZF1, IL16, IL18RAP, IL1R2, IL1 RN, IL2RG, IL32, ILVBL, IMPDH1, INPP5D, IPO5, ITGA2B, ITGAL, ITGAM, ITGAX, ITGB2, ITGB4, JAK3, JUND, JUP, KCNAB2, KCNE1, KIAA1191, KIFC1, KLF1, LAD1, LAMB2, LAMC2, LAPTM5, LCP2, LDHA, LGALS3BP, LGALS4, LGMN, LILRA1, LILRA5, LILRB2, LILRB3, LIMD2, LIPH, LMNB1, LMO7, LPAR2, LRCH4, LRRC25, LSP1, LSR, LST1, LTB, LYL1, MACROD1, MAGED1, MAN2A2, MAP1LC3A, MEFV, MEP1A, MFAP4, MIS18A, MISP, MKNK1, MLKL, MMAB, MME, MMP11, MMP25, MMP7, MMP8, MORN2, MPO, MPP1, MPZL2, MRPL17, MSL3, MSRB1, MTIF2, MUC13, MX2, MXD3, MYL4, MYO1A, MYO1F, MYO1G, MZT2A, NABP1, NADK, NAIP, NAMPT, NARF, NBEAL2, NCF1, NCF2, NCF4, NDEL1, NDUFAF4, NDUFB5, NEK2, NFAM1, NFE2, NKG7, NLRC4, NLRC5, NLRP12, NNMT, NOX1, NQO1, NTMT1, NTPCR, NUPR1, OAZ1, ORM1, OSCAR, P2RX1, PADI2, PADI4, PALLD, PARVG, PDHA1, PDHX, PGD, PGLYRP1, PHC2, PHF21A, PHGR1, PHOSPHO1, PIK3R5, PIN4, PLB1, PLBD1, PLCB2, PLCD3, PLCG2, PLEKHA1, PLS3, POF1B, POLR2H, POSTN, PPBP, PPIL1, PPM1M, PPP1R16A, PPP1R1B, PRAM1, PRAP1, PREX1, PRKCB, PROCR, PROK2, PRR15, PRR15L, PRRC1, PRSS22, PRSS8, PRTN3, PSTPIP1, PTK2B, PTPN6, PYCR1, PYGL, R3HDM4, RAB24, RAB25, RAC2, RARRES2, RASAL3, RASGRP2, RASGRP4, RASSF2, REG4, RELT, REM2, RETN, RFC3, RGL4, RGS19, RHOD, RHPN2, RIN3, RNASE4, RND3, RNF166, RNF167, RPL41, RPS6KA1, RPS9, S100A12, S100A14, S100A8, S1PR4, SAP25, SASH3, SCNN1A, SCOC, SDCBP2, SEC11C, SECTM1, SELL, SEMA4D, SEPP1, SEPTIN10, SFN, SHKBP1, SIGLEC5, SIPA1, SIRPB1, SLC11A1, SLC12A9, SLC16A3, SLC25A37, SLC2A3, SLC2A8, SLC38A5, SLC39A5, SLC43A2, SLCO3A1, SMAP2, SMIM22, SNCA, SORD, SORL1, SPATS2L, SPI1, SRC, ST20, STAP2, STARD10, STAT5B, STEAP1, STK10, STX11, STXBP2, SULT2B1, SYTL3, TACC3, TAGAP, TALDO1, TBC1 D10C, TBX21, TBXAS1, TCEAL4, TFF3, THBS2, THEMIS2, TIMM8B, TINAGL1, TJP3, TLR6, TM4SF5, TMBIM6, TMC4, TMCC2, TMEM106C, TMEM126B, TMEM14A, TMEM14C, TMEM71, TMEM91, TMEM97, TMPRSS2, TMPRSS4, TNFRSF10C, TNS3, TOP2A, TPM1, TRAF3IP3, TREM1, TREML2, TRIM22, TRIM25, TSKU, TSPAN15, TSPAN8, TUBA4A, TUBB1, TYMS, TYROBP, UBE2C, UBE2D3, UBE2T, UGT8, UNC13D, UQCC2, URI1, USB1, USH1C, VARS, VASP, VAV1, VMP1, VNN2, VNN3, VPS51, VSTM1, VWA1, WAS, WDR12, WFS1, XPO6, ZAP70, ZDHHC18, ZDHHC19, ZDHHC9, ZNF467, ZWINT and parts thereof.

In some embodiments, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR, SLC11A1, NLRP12, HMBS, LILRB3, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof. In some embodiments, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof. In some embodiments, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.

In various embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with a specific cancer type or a specific group of cancers, the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ABTB1, ACAP1, ACO1, ACSL1, ADIRF, AGR2, AGR3, AK2, AKNA, ALDH18A1, ANKS4B, ARAP1, ARHGAP25, ARHGAP30, ARHGAP9, ARHGEF16, ARHGEF35, ARIDSA, ARRB2, ARSE, ATG16L2, ATP2A2, ATP2C2, ATP5G1, ATP5G3, AXIN2, AZGP1, B3GNT3, BATF2, BCAR1, BCL2L15, BCL2L2, BCL6, BDH1, BDH2, BEST1, BGN, BIN2, BIRCS, BMP4, BOK, BSPRY, C10orf54, C11orf21, C16orf54, C19orf33, C1orf162, C1orf210, C1QTNF5, C3, C5AR2, C6orf203, C8orf59, CA1, CALD1, CAMP, CAPNS, CCL20, CCM2, CCR7, CD177, CD276, CD300LF, CD37, CD44, CD55, CDC42SE1, CDCP1, CDH1, CDH17, CDHRS, CDK4, CDK5RAP2, CDX1, CEACAM1, CEACAM4, CEACAM5, CENPF, CFD, CFTR, CHCHD6, CHID1, CKB, CKMT1B, CLDN7, CLEC4E, CORO1A, COTL1, COX6C, CR1, CRB3, CSF3R, CTGF, CTNND1, CXCR1, CXCR2, DDC, DDR1, DDX10, DENND1C, DMTN, DOK3, DPEP2, ECT2, EEF1E1, EFNA3, E124, ELF3, EMP1, ENTPD2, ENTPD6, EPCAM, EPHA2, EPS8L3, ERBB2, ERBB3, EVI2B, F3, FAM101A, FAM109A, FAM212B, FAM213B, FAM60A, FAM65B, FAM83E, FAM84A, FBL, FBXL5, FCAR, FCGR2A, FCN1, FERMT1, FFAR2, FGD3, FGFR4, FGFRL1, FGR, FMNL1, FN1, FOLR3, FOXA2, FPR1, FUT2, FUT6, GATA1, GBP3, GGT6, GJB2, GLRX3, GLT1D1, GMFG, GMNN, GNLY, GOLT1A, GPC4, GPR35, GPRCSA, GPX2, GRTP1, GZMH, H2AFY2, HBB, HBD, HBG2, HBM, HBQ1, HCK, HID1, HK3, HKDC1, HMGB3, HMGCS2, HN1L, HNF4A, HTRA1, ICAM3, IFITM1, IFITM2, IFT172, IKZF1, IL1R2, IL1 RN, IL32, ILVBL, IPO5, ITGA2B, ITGAM, ITGB4, JUND, JUP, KIAA1191, KIFC1, LAD1, LAMB2, LAMC2, LDHA, LGALS3BP, LGALS4, LGMN, LILRB2, LILRB3, LIMD2, LIPH, LMNB1, LMO7, LRRC25, LSR, LST1, MACROD1, MAGED1, MAP1LC3A, MEP1A, MFAP4, MIS18A, MISP, MKNK1, MMAB, MME, MMP11, MMP25, MMP7, MMP8, MORN2, MPP1, MPZL2, MRPL17, MSRB1, MTIF2, MUC13, MXD3, MYL4, MYO1A, MYO1F, MZT2A, NAMPT, NCF1, NCF2, NCF4, NDUFAF4, NDUFB5, NEK2, NFAM1, NFE2, NKG7, NNMT, NOX1, NQO1, NTMT1, NTPCR, NUPR1, OAZ1, ORM1, OSCAR, P2RX1, PADI4, PALLD, PDHA1, PDHX, PGLYRP1, PHC2, PHGR1, PHOSPHO1, PIK3R5, PIN4, PLCD3, PLEKHA1, PLS3, POF1B, POLR2H, POSTN, PPIL1, PPM1M, PPP1R16A, PPP1R1B, PRAM1, PRAP1, PRKCB, PROCR, PRR15, PRR15L, PRRC1, PRSS22, PRSS8, PRTN3, PSTPIP1, PTPN6, PYCR1, RAB25, RARRES2, RASGRP2, RASGRP4, RASSF2, REG4, RETN, RFC3, RHOD, RHPN2, RIN3, RNASE4, RND3, RPL41, RPS6KA1, RPS9, S100A12, S100A14, S100A8, S1PR4, SCNN1A, SCOC, SDCBP2, SEC11C, SEPP1, SEPTIN10, SFN, SHKBP1, SIGLEC5, SIRPB1, SLC11A1, SLC25A37, SLC2A8, SLC39A5, SMIM22, SNCA, SORD, SPATS2L, SPI1, SRC, STAP2, STARD10, STEAP1, STX11, SULT2B1, SYTL3, TBC1D10C, TCEAL4, TFF3, THBS2, THEMIS2, TIMM8B, TINAGL1, TJP3, TM4SF5, TMBIM6, TMC4, TMEM106C, TMEM126B, TMEM14A, TMEM14C, TMEM71, TMEM91, TMEM97, TMPRSS2, TMPRSS4, TNFRSF10C, TNS3, TOP2A, TPM1, TRAF3IP3, TREM1, TRIM22, TSKU, TSPAN15, TSPAN8, TYMS, TYROBP, UBE2C, UBE2T, UGT8, UQCC2, URI1, USH1C, VARS, VAV1, VMP1, VNN2, VPS51, VSTM1, VWA1, WAS, WDR12, WFS1, XPO6, ZAP70, ZDHHC19, ZDHHC9, ZNF467 and ZWINT.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with a specific cancer type or a specific group of cancers, the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ACAP1, ACSL1, ADIRF, ANKS4B, ARHGAP30, ARSE, ATP5G3, BCAR1, BCL6, BGN, BIN2, BMP4, C19orf33, C1orf162, C5AR2, CCR7, CD276, CD37, CD44, CDC42SE1, CDH17, CDK5RAP2, CHCHD6, CKB, CLDN7, CLEC4E, CTGF, DDX10, ELF3, ERBB3, F3, FAM101A, FAM65B, FAM84A, FBXL5, FCAR, FCN1, FERMT1, FFAR2, FOLR3, FOXA2, FUT2, GMFG, GPRC5A, GPX2, HBB, HBD, HID1, LAMC2, LDHA, LGALS4, LGMN, LIMD2, LRRC25, LSR, MAGED1, MPZL2, MRPL17, MXD3, MYO1A, NCF1, NCF2, NFE2, OAZ1, PHOSPHO1, PLCD3, POF1B, POSTN, PPP1R16A, PRAP1, PRR15L, PRSS8, PRTN3, RAB25, RASGRP4, RFC3, S100A12, SCOC, SDCBP2, SEPP1, SHKBP1, SLC11A1, SORD, SRC, STAP2, STARD10, STX11, SYTL3, TCEAL4, TFF3, TM4SF5, TMC4, TMEM126B, TMPRSS2, TNFRSF10C, TRAF3IP3, TREM1, TRIM22, TYMS, TYROBP, UBE2C, UGT8, UQCC2, VAV1, VNN2, WAS and ZDHHC9.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with a specific cancer type or a specific group of cancers, the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ACSL1, ANKS4B, ARHGAP30, ATP5G3, B3GNT3, BCL6, BIN2, BMP4, C19orf33, C1orf162, CD37, CLEC4E, ERBB3, FBXL5, FCAR, FCN1, FERMT1, FFAR2, FOXA2, GMFG, HBB, HID1, ICAM3, LGALS4, LGMN, LSR, MXD3, MYO1A, NCF1, NCF2, NFE2, OAZ1, PHOSPHO1, PLCD3, PRAP1, PRSS8, PRTN3, RAB25, RASGRP4, SCOC, SDCBP2, SEPP1, SHKBP1, SYTL3, TFF3, TM4SF5, TMC4, TMPRSS2, TRAF3IP3, TRIM22, TYROBP, UGT8, VAV1 and WAS.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with a specific cancer type or a specific group of cancers, the NDR comprises the following: first exon-intron junction of SHKBP1, first exon-intron junction of ACSL1, first exon-intron junction of BCAR1, promoter of RAB25, promoter of PRTN3 and/or promoter of LSR.

In some embodiments, the method further comprises assigning the most weight to the level of cfDNA that maps to the first exon-intron junction of SHKBP1 and less weight to the level of cfDNA that maps to the other NDR(s) when estimating the ctDNA burden. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the first exon-intron junction of SHKBP1 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the first exon-intron junction of ACSL1, the first exon-intron junction of BCAR1, the promoter of RAB25, the promoter of LSR and the promoter of PRTN3. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the first exon-intron junction of ACSL1 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the first exon-intron junction of BCAR1, the promoter of RAB25, the promoter of LSR and the promoter of PRTN3. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the first exon-intron junction of BCAR1 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of RAB25, the promoter of LSR and the promoter of PRTN3. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of RAB25 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of LSR and the promoter of PRTN3. In various embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of LSR and relatively less weight to the level of cfDNA that maps to the promoter of PRTN3. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to a first exon-intron junction and relatively less weight to the level of cfDNA that maps to a promoter.

In various embodiments, the specific cancer type or specific group of cancers comprises colorectal cancer.

In various embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with any cancer or cancer in general (pan cancer), the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ABHD5, ABTB1, ACAP1, ACRBP, ACSL1, ADAM8, AHSP, AKNA, ALAS2, ALOX5, ANPEP, AOAH, APOBEC3A, ARAP1, ARHGAP26, ARHGAP9, ARID5A, ARRB2, ATG16L2, ATP6V1B2, AZU1, BIN2, BMX, BPI, BTK, BTNL8, C11orf21, C19orf35, C1orf162, C1orf228, C6orf25, CA1, CA4, CAMP, CARS2, CCDC88B, CCND3, CD177, CD244, CD300E, CD300LB, CD37, CD44, CD53, CDK5RAP2, CEACAM3, CEACAM4, CELF2, CFP, CLC, CLEC12A, CLEC4D, CLEC4E, CMTM2, CNN2, CORO1A, CORO7, CR1, CSF3R, CXCR1, CXCR2, CYBA, CYTH4, DEF8, DEFA1, DEFA1B, DEFA3, DEFA4, DENND1C, DENND3, DHRS13, DHX34, DMTN, DNAH17, DOCK2, DOK3, DYSF, ECE1, EGLN2, ELANE, EPB42, FAM49B, FAM65B, FBXL5, FCAR, FCGR2A, FCGR3B, FCN1, FERMT3, FES, FFAR2, FGD3, FGR, FKBP8, FLOT2, FMNL1, FOLR3, FPR2, FUT7, GATA1, GCA, GNG2, GNLY, GP9, GPSM3, GRAMD1A, GRAP2, HBA1, HBA2, HBB, HBD, HBG1, HBG2, HBM, HBQ1, HCK, HCLS1, HK3, HMBS, ICAM3, IFI30, IFITM1, IFITM2, IL16, IL18RAP, IL1R2, IL2RG, IMPDH1, INPP5D, ITGA2B, ITGAL, ITGAM, ITGAX, ITGB2, JAK3, KCNAB2, KCNE1, KLF1, LAPTM5, LCP2, LILRA1, LILRA5, LILRB2, LILRB3, LPAR2, LRCH4, LSP1, LST1, LTB, LYL1, MAN2A2, MEFV, MKNK1, MLKL, MMP25, MMP8, MPO, MPP1, MSL3, MSRB1, MX2, MXD3, MYL4, MYO1F, MYO1G, NABP1, NADK, NAIP, NAMPT, NARF, NBEAL2, NCF1, NCF2, NDEL1, NFE2, NLRC4, NLRC5, NLRP12, P2RX1, PADI2, PADI4, PARVG, PGD, PGLYRP1, PHF21A, PHOSPHO1, PIK3R5, PLB1, PLBD1, PLCB2, PLCG2, PPBP, PRAM1, PREX1, PROK2, PRTN3, PSTPIP1, PTK2B, PTPN6, PYGL, R3HDM4, RAB24, RAC2, RASAL3, RASGRP2, RASGRP4, RELT, REM2, RGL4, RGS19, RIN3, RNF166, RNF167, SAP25, SASH3, SECTM1, SELL, SEMA4D, SHKBP1, SIGLEC5, SIPA1, SIRPB1, SLC11A1, SLC12A9, SLC16A3, SLC2A3, SLC38A5, SLC43A2, SLCO3A1, SMAP2, SORL1, SPI1, ST20, STAT5B, STK10, STXBP2, TACC3, TAGAP, TALDO1, TBC1D10C, TBX21, TBXAS1, THEMIS2, TLR6, TMCC2, TMEM71, TNFRSF10C, TRAF3IP3, TREML2, TRIM25, TUBA4A, TUBB1, UBE2D3, UNC13D, USB1, VASP, VAV1, VMP1, VNN3, VSTM1, WAS, XPO6, ZAP70, ZDHHC18 and ZDHHC19.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with any cancer or cancer in general (pan cancer), the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ABTB1, ACAP1, ACSL1, ARHGAP9, ATG16L2, ATP6V1B2, BIN2, BTK, BTNL8, C19orf35, CA4, CD37, CDK5RAP2, CEACAM4, CFP, CLEC12A, CLEC4D, CLEC4E, CSF3R, CXCR2, CYTH4, DEF8, DENND1C, DENND3, DHRS13, DOK3, FAM49B, FBXL5, FCGR2A, FCN1, FES, FFAR2, FKBP8, FMNL1, FOLR3, FUT7, GNG2, GP9, GPSM3, HBD, HK3, HMBS, IFI30, IL16, IL1R2, ITGA2B, JAK3, KCNE1, LCP2, LILRB2, LILRB3, LYL1, MAN2A2, MKNK1, MLKL, MPO, MX2, MYO1F, NCF1, NFE2, NLRP12, PADI2, PADI4, PARVG, PGLYRP1, PHOSPHO1, PREX1, PRTN3, PSTPIP1, RAC2, RASAL3, RASGRP4, RELT, RNF166, RNF167, SHKBP1, SLC11A1, SLC12A9, SLC16A3, SLCO3A1, SORL1, SPI1, TBC1D10C, TBXAS1, USB1, VAV1, VSTM1, XPO6 and ZDHHC18.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden associated with any cancer or cancer in general (pan cancer), the NDR comprises one or more, or at least about one, at least about two, at least about three, at least about four, at least about five, at least about six, at least about seven, at least about eight, at least about nine, or at least about ten of the following genes/associated NDRs (e.g. a transcription start site, a promoter, an intron-exon junction and/or an exon-intron junction): ABTB1, ACAP1, ACSL1, ATG16L2, ATP6V1B2, BTK, BTNL8, C19orf35, CEACAM4, CLEC4E, CSF3R, DENND1C, DENND3, DHRS13, FBXL5, FCAR, FCN1, FFAR2, FKBP8, FMNL1, GNG2, GP9, GPSM3, HBD, HMBS, IFI30, IL18RAP, ITGA2B, LCP2, LILRB3, LYL1, MAN2A2, MKNK1, MPO, MX2, MXD3, MYO1F, NFE2, NLRP12, PADI4, PHOSPHO1, PREX1, RASGRP2, RASGRP4, RGL4, RNF166, RNF167, SHKBP1, SLC11A1, SLC12A9, TBC1 D10C, TBXAS1, USB1 and VSTM1.

In some embodiments, where the method comprises a method of estimating a ctDNA burden or tumor burden with any cancer or cancer in general (pan cancer), the NDR comprises the following: promoter of SLC11A1, promoter of NLRP12, promoter of PRTN3, promoter of HMBS, promoter of LILRB3, first exon-intron junction of ACSL1, first exon-intron junction of GP9, promoter of MX2, promoter of RASGRP4 and/or promoter of ATG16L2.

In some embodiments, the method further comprises assigning the most weight to the level of cfDNA that maps to the promoter of HMBS and/or the first exon-intron junction of GP9 and relatively less weight to the level of cfDNA that maps to the other NDR(s) when estimating the ctDNA burden. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of HMBS and/or the first exon-intron junction of GP9 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of RASGRP4, the promoter of NLRP12, the promoter of ATG16L2, the promoter of SLC11A1, the promoter of LILRB3, the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of RASGRP4 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of NLRP12, the promoter of ATG16L2, the promoter of SLC11A1, the promoter of LILRB3, the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of NLRP12 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of ATG16L2, the promoter of SLC11A1, the promoter of LILRB3, the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of ATG16L2 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of SLC11A1, the promoter of LILRB3, the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of SLC11A1 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of LILRB3, the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of LILRB3 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of PRTN3, the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning more weight to the level of cfDNA that maps to the promoter of PRTN3 and relatively less weight to the level of cfDNA that maps to one or more of the following NDRs: the promoter of MX2 and the first exon-intron junction of ACSL1. In some embodiments, the method comprises assigning similar weights to the level of cfDNA that maps to the promoter of HMBS and the level of cfDNA that maps to the first exon-intron junction of GP9. In some embodiments, the method comprises assigning similar weights to the level of cfDNA that maps to the promoter of MX2 and the level of cfDNA that maps to the first exon-intron junction of ACSL1.

In various embodiments, the total length/size of the one or more NDR is no more than about 100 kilobase pairs (kb), no more than about 90 kb, no more than about 80 kb, no more than about 70 kb, no more than about 60 kb, no more than about 50 kb, no more than about 30 kb, no more than about 20 kb or more than about 10 kb. In some embodiments, the total length/size of the one or more NDR is no more than about 30 kb. In some embodiments, the total length/size of the one or more NDR is no more than about 25 kb. In some embodiments, the total length/size of the one or more NDR is about 24 kb.

In various embodiments, the method does not comprise sequencing one or more regions that collectively spans more than about 100 kb, more than about 95 kb, more than about 90 kb, more than about 85 kb, more than about 80 kb, more than about 75 kb, more than about 70 kb, more than about 65 kb, more than about 60 kb, more than about 55 kb, more than about 50 kb, more than about 45 kb, more than about 40 kb, more than about 35 kb, more than about 30 kb, more than about 25 kb, more than about 20 kb, more than about 15 kb, more than about 10 kb or more than about 5 kb in length. In various embodiments, the method does not comprise sequencing a continuous/contiguous region that spans more than about 4 kb, more than about 5 kb, more than about 6 kb, more than about 7 kb, more than about 8 kb, more than about 9 kb or more than about 10 kb in length. In various embodiments, the method does not comprise whole genome sequencing of the cfDNA. Advantageously, embodiments of the method are efficient in terms of time and resources, and provide a fast turnaround time.

As may be appreciated, by following the teachings herein/carrying out the steps of this disclosure, a person skilled in the art will also be able to identify further genomic regions (including non-coding regions), other than the ones highlighted in this disclosure, that are also predictive of the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, an amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and the ctDNA content. Hence, the genes/regions highlighted in this disclosure are non-exhaustive. Indeed, a person skilled in the art would understand that the genomic regions that may be used to predict the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, an amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content are not limited to the particular gene-encoding regions described herein, and may also include non-coding regions (including regions that are far away from genes e.g. regulatory regions such as enhancers).

In various embodiments, the method further comprises removing particulate blood components from the sample (e.g. a blood sample) to leave behind blood plasma for use in the determining step. In various embodiments, plasma is separated from blood shortly after (e.g. within about 2 hours of) venipuncture. In various embodiments, plasma is separated from blood by centrifugation e.g. at 10 min×300 g and 10 min×9370 g). In various embodiments, the plasma is stored at low temperature e.g. at −80° C. after separation. In various embodiments, the particulate blood components are selected from the group consisting red blood cells, white blood cells, platelets and combinations thereof. In various embodiments, the method further comprising extracting/isolating/purifying the cfDNA from the sample/blood plasma.

In various embodiments, the method requires no more than about 20 milliliters, no more than about 19.5 milliliters, no more than about 19 milliliters, no more than about 18.5 milliliters, no more than about 18 milliliters, no more than about 17.5 milliliters, no more than about 17 milliliters, no more than about 16.5 milliliters, no more than about 16 milliliters, no more than about 15.5 milliliters, no more than about 15 milliliters, no more than about 14.5 milliliters, no more than about 14 milliliters, no more than about 13.5 milliliters, no more than about 13 milliliters, no more than about 12.5 milliliters, no more than about 12 milliliters, no more than about 11.5 milliliters, no more than about 11 milliliters, no more than about 10.5 milliliters, no more than about 10 milliliters, no more than about 9.5 milliliters, no more than about 9 milliliters, no more than about 8.5 milliliters, no more than about 8 milliliters, no more than about 7.5 milliliters, no more than about 7 milliliters, no more than about 6.5 milliliters, no more than about 6 milliliters, no more than about 5.5 milliliters, no more than about 5 milliliters, no more than about 4.5 milliliters, no more than about 4 milliliters, no more than about 3.5 milliliters, no more than about 3 milliliters, no more than about 2.5 milliliters, no more than about 2 milliliters, no more than about 1.5 milliliters, no more than about 1 milliliters, no more than about 0.9 milliliters, no more than about 0.8 milliliters, no more than about 0.7 milliliters, no more than about 0.6 milliliters, no more than about 500 microliters, no more than about 450 microliters, no more than about 400 microliters, no more than about 350 microliters or no more than about 300 microliters of sample.

In various embodiments, the method further comprises obtaining the sample from the subject prior to the determining step. In various embodiments, the step of obtaining the sample from the subject is a non-surgical step, a non-invasive step or a minimally invasive step. In various embodiments, the step of obtaining the sample from the subject comprises withdrawing a blood sample from the subject.

In various embodiments, the method is capable of precisely estimating one or more of: a disease burden, a cancer burden, a tumor burden, a ctDNA burden, a level of ctDNA, an amount of ctDNA, a proportion of ctDNA, a fraction of ctDNA and a ctDNA content such that the estimated disease burden, cancer burden, tumor burden, ctDNA burden, level of ctDNA, amount of ctDNA, proportion of ctDNA, fraction of ctDNA and/or ctDNA content has an absolute deviation/absolute error/mean absolute deviation/mean absolute error of no more than about 5.0%, no more than about 4.9%, no more than about 4.8%, no more than about 4.7%, no more than about 4.6%, no more than about 4.5%, no more than about 4.4%, no more than about 4.3%, no more than about 4.2%, no more than about 4.1%, no more than about 4.0%, no more than about 3.9%, no more than about 3.8%, no more than about 3.7%, no more than about 3.6%, no more than about 3.5%, no more than about 3.4%, no more than about 3.3%, no more than about 3.2%, no more than about 3.1%, no more than about 3%, no more than about 2.9%, no more than about 2.8%, no more than about 2.7%, no more than about 2.6%, no more than about 2.5%, no more than about 2.4%, no more than about 2.3%, no more than about 2.2%, no more than about 2.1%, no more than about 2%, no more than about 1.9%, no more than about 1.8%, no more than about 1.7%, no more than about 1.6%, or no more than about 1.5% from a true/expected/measured disease burden, cancer burden, tumor burden, ctDNA burden, level of ctDNA, amount of ctDNA, proportion of ctDNA, fraction of ctDNA and/or ctDNA content.

In various embodiments, the method has a predictive accuracy of at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.1%, at least about 99.2%, at least about 99.3%, at least about 99.4%, at least about 99.5%, at least about 99.6%, at least about 99.7%, at least about 99.8%, at least about 99.9% or at least about 100%.

In various embodiments, the method comprises a machine learning-based method.

In various embodiments, the method further comprises training a machine learning model with a first training data set defining a level (or an amount, a proportion, a fraction and/or a content) of DNA, optionally cfDNA, that maps to (or aligns with, corresponds to, belongs to, is similar to and/or is identical to) the one or more NDR (e.g. in the form of a read depth coverage) as features and a measured disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content; and selecting a first set of one or more features that is predictive of the disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content.

In various embodiments, a subset of samples may be randomly selected from a training data set to train the machine learning model to identify the most predictive features. In various embodiments, the foregoing may be repeated independently multiple times, e.g. 1000 times, and the time(s) each feature is chosen as a predictive feature is counted. In various embodiments, the feature(s) that is/are selected most frequently is/are extracted to train a final model comprising all samples in the training data set (e.g. the first training data set) to identify one or more features (e.g. the first set of one or more features) that is predictive of the disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content. In various embodiments, cross validation (e.g. five-fold cross validation, eight-fold cross validation, ten-fold cross validation) is carried out during the machine learning process for identifying the most predictive features.

In various embodiments, the selecting step further comprises employing a linear model/regression, optionally a sparse linear model/regression, further optionally a Lasso (least square absolute shrinkage and selection operator) model to identify the first set of one or more features that is predictive of the disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content.

In various embodiments, the method further comprises providing a test data set to the trained machine learning model, the test data set defining at least the first set of one or more selected features; and estimating the disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content based on at least the first set of one or more selected features.

In various embodiments, the method further comprises comparing the estimated disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content with a true/expected/measured disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content of the test data set; and calculating an absolute deviation/absolute error/mean absolute deviation/mean absolute error between the estimated and the true/expected/measured disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content to evaluate a performance/prediction accuracy of the model.

In various embodiments, the method further comprises obtaining/collecting blood samples comprising cfDNA from cancer patients and healthy individuals; measuring a level (or an amount, a proportion, a fraction and/or a content) of DNA that maps to (or aligns with, corresponds to, belongs to, is similar to and/or is identical to) the one or more NDR (e.g. in the form of a read depth coverage) to obtain the features of the first training data set; and measuring a disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content (e.g. by whole genome sequencing, deep whole genome sequencing etc.) to obtain the disease burden/tumor burden/ctDNA burden/ctDNA level/ctDNA amount/ctDNA proportion/ctDNA fraction/ctDNA content of the first training data set. In various embodiments, the method further comprises determining/measuring an expression of the plurality of genes associated with the NDR in the blood samples.

In various embodiments, the method further comprises obtaining/collecting tumor/tumor biopsy samples from cancer patients; extracting/isolating/purifying nucleic acids from the tumor/tumor biopsy samples; measuring from the nucleic acids a level (or an amount, a proportion, a fraction and/or a content) of DNA that maps to (or aligns with, corresponds to, belongs to, is similar to and/or is identical to) the one or more NDR (e.g. in the form of a read depth coverage); and measuring from the nucleic acids an expression of the genes associated with the one or more NDR in the tumor/tumor biopsy samples.

In various embodiments, the method further comprises comparing said level (or an amount, a proportion, a fraction and/or a content) of DNA (e.g. in the form of a read depth coverage) and/or the expression of the genes between the blood samples and the tumor/tumor biopsy samples; identifying genes that show substantially different level (or an amount, a proportion, a fraction and/or a content) of DNA (e.g. substantially different read depth coverages) and/or substantially different expressions between the blood samples and the tumor/tumor biopsy samples; and selecting the level (or an amount, a proportion, a fraction and/or a content) of DNA (e.g. in the form of a read depth coverage) of these identified genes in the blood sample as features to be input in the first training data set.

The method may further comprise removing the first set of one or more features from the first training data set to form a second training data set; and training the machine learning model with the second training data set to select a second set of one or more features that is predictive of the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, an amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content. These steps may be repeated one or more times to obtain a third, fourth, fifth etc. set of one or more features that is predictive of the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, an amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content by removing the second, third, fourth etc. set of one or more features from the second, third, fourth etc. training data set to form a third, fourth, fifth etc. training data set respectively.

In various embodiments, the method further comprises screening for/detecting a tumor-specific mutation in the cfDNA/ctDNA present in the blood sample. Advantageously, embodiments of the method simultaneously allow for profiling of actionable cancer mutations and quantitative estimation of the disease burden, the cancer burden, the tumor burden, the ctDNA burden, the level of ctDNA, an amount of ctDNA, the proportion of ctDNA, the fraction of ctDNA and/or the ctDNA content. The method may be performed in combination with or complimentary to existing sequencing-based methods in cancer detection/monitoring.

In various embodiments, the method is an in vitro or ex vivo method.

In various embodiments, the method is a liquid biopsy method.

In various embodiments, the method is a method of determining disease progression in a subject and the method further comprises: determining in a subsequent blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR; estimating the ctDNA burden or tumor burden based on said level of cfDNA; comparing the ctDNA burden or tumor burden estimated from said subsequent blood sample with the ctDNA burden or tumor burden estimated from said blood sample; and optionally identifying the subject as having disease progression if the ctDNA burden or tumor burden estimated from said subsequent blood sample is higher than the ctDNA burden or tumor burden estimated from said blood sample or identifying otherwise if the ctDNA burden or tumor burden estimated from said subsequent blood sample is not higher than the ctDNA burden or tumor burden estimated from said blood sample. In various embodiments, where the ctDNA burden or tumor burden estimated from said subsequent blood sample is lower than the ctDNA burden or tumor burden estimated from said blood sample, the disease identified to be improving/abating in the subject. In various embodiments, where the ctDNA burden or tumor burden estimated from said subsequent blood sample is substantially the same as the ctDNA burden or tumor burden estimated from said blood sample, the disease is identified to be stable in the subject.

Disease progression in a subject may be indicative of resistance to the current treatment regimen received by the subject. Thus, the method may also be useful for identifying resistance to treatment in a subject. In various embodiments therefore, the method further comprises changing the treatment regimen received by the subject if the subject is identified as having disease progression. Changing the treatment regimen may involve subjecting/exposing the subject to a second therapy that is different from the current or the first therapy. Changing the treatment regimen may involve replacing the current treatment regimen received by the subject with another treatment regimen, or it may involve administering to the subject additional therapies in addition to the current treatment regimen. In some embodiments, where a subject is already receiving combination therapy, changing the treatment regimen may also involve removing one or more therapies from the combination therapy. Examples of treatment regimens/therapies include, but are not limited to, chemotherapy, radiotherapy, gene therapy, hormonal therapy, immunotherapy, surgical therapy, combination therapy, alternative therapy/complementary therapy and combinations thereof. In various embodiments, changing the treatment regimen does not necessarily entail switching from one class of therapy (e.g. one of chemotherapy, radiotherapy, gene therapy, hormonal therapy, immunotherapy, surgical therapy, combination therapy, alternative therapy/complementary therapy and combinations thereof) to another class of therapy, although it may involve such a switch. Changing the treatment regimen may involve changing from one specific therapy to another specific therapy within the same therapy class. For example, changing the treatment regimen may involve changing the particular chemotherapy drug received by the subject.

In various embodiments, there is provided a method of monitoring disease progression in a subject, the method comprising: determining in a first sample comprising cfDNA obtained from the subject at a first time point, a first level (or an amount, a proportion, a fraction and/or a content) of cfDNA that maps to one or more NDR; estimating a first ctDNA burden or tumor burden (or a disease burden, a cancer burden, a level of ctDNA, an amount of ctDNA, a proportion of ctDNA, a fraction of ctDNA and a ctDNA content) in the subject based on the first level of cfDNA, determining in a second sample comprising cfDNA obtained from the subject at a second time point, a second level of DNA that maps to the one or more NDR, estimating a second ctDNA burden or tumor burden based on the second level of cfDNA; and comparing the first and the second estimated ctDNA burden or tumor burden to determine whether the disease has progressed, wherein the second time point is later than the first time point. In various embodiments, where the second estimated ctDNA burden or tumor burden is higher than the first estimated ctDNA burden or tumor burden, the disease is considered to have progressed/worsened. In various embodiments, where the second estimated ctDNA burden or tumor burden is lower than or is substantially the same as the first estimated ctDNA burden or tumor burden, the disease is considered to have abated or stabilized.

In various embodiments, there is provided a method of evaluating treatment efficacy/response in a subject, the method comprising: determining in a first sample comprising cfDNA obtained from the subject before/during a treatment/treatment stage, a first level (or an amount, a proportion, a fraction and/or a content) of cfDNA that maps to one or more NDR; estimating a first ctDNA burden or tumor burden (or a disease burden, a cancer burden, a level of ctDNA, an amount of ctDNA, a proportion of ctDNA, a fraction of ctDNA and a ctDNA content) in the subject based on the first level of cfDNA, determining in a second sample comprising cfDNA obtained from the subject after the treatment/treatment stage, a second level of DNA that maps to the one or more NDR, estimating a second ctDNA burden or tumor burden based on the second level of cfDNA; and comparing the first and the second estimated ctDNA burden or tumor burden to determine whether the treatment is effective/the subject is responding to the treatment. In various embodiments, where the second estimated ctDNA burden or tumor burden is higher than the first estimated ctDNA burden or tumor burden, the treatment is considered to be not effective or the subject is considered to be not responding to the treatment. In various embodiments, where the treatment is considered to be not effective or the subject is considered to be not responding to the treatment, the method further comprises adjusting/altering/stopping/halting/discontinuing the treatment regimen. In various embodiments, where the second estimated ctDNA burden or tumor burden is lower than or substantially the same as the first estimated ctDNA burden or tumor burden, the treatment is considered to be effective or the subject is considered to be responding to the treatment. In various embodiments, where the treatment is considered to be effective or the subject is considered to be responding to the treatment, the method further comprises continuing the treatment regimen.

In various embodiments, there is provided a method of determining a risk of cancer (e.g. a risk of development, predisposition, progression, relapse, recurrence, metastasis, abatement of cancer) in a subject, the method comprising: determining in a blood sample obtained from the subject, a level (or an amount, a proportion, a fraction and/or a content) of cfDNA that maps to one or more NDR, optionally estimating a disease burden (or a cancer burden, a tumor burden, a ctDNA burden, a level of ctDNA, an amount of ctDNA, a proportion of ctDNA, a fraction of ctDNA or a ctDNA content) based on said level of cfDNA, and determining the risk of cancer based on the level of cfDNA that maps to the one or more NDR, or the estimated disease burden. In various embodiments, where the level of cfDNA/the estimated disease burden exceeds a predetermined threshold level, the subject is concluded to have an elevated risk of cancer. In various embodiments, where the level of cfDNA/the estimated disease burden does not exceed the predetermined threshold level, the subject is concluded to have a reduced/low/minimal/no risk of cancer. It will be appreciated that it is within the purview of a person skilled in the art to determine the suitable threshold level. For example, the suitable threshold level may be determined by determining the mean level of cfDNA/the mean estimated disease burden of a healthy population e.g. a population that does not suffer from cancer.

In various embodiments, there is provided a method of treating cancer in a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR and estimating a ctDNA burden or tumor burden based on said level of cfDNA. In various embodiments, where the level of cfDNA/the estimated ctDNA burden or tumor burden exceeds a predetermined threshold level, the subject is subjected to treatment selected from the group consisting of chemotherapy, radiotherapy, gene therapy, hormonal therapy, immunotherapy, surgical therapy, combination therapy, alternative therapy/complementary therapy and combinations thereof. It will be appreciated that it is within the purview of a person skilled in the art to determine the suitable threshold level. For example, the suitable threshold level may be determined by determining the mean level of cfDNA/the mean estimated ctDNA burden or tumor burden of a healthy population e.g. a population that does not suffer from cancer.

In various embodiments, there is provided a method of profiling a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR and estimating a ctDNA burden or tumor burden based on said level of cfDNA.

In various embodiments, there is provided a kit/panel/probe set/primer set, optionally a kit/panel/probe set/primer set for estimating a tumor burden or ctDNA burden in a subject, the kit/panel/probe set/primer set comprising one or more probe/primer that is capable of hybridizing/binding to one or more NDR, where said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood tissue and tumor tissue and/or (ii) is degraded to different extents between healthy blood tissue and blood tissue of a tumor-bearing subject. In various embodiments, the one or more probe/primer is capable of hybridizing/binding to a central genomic region related to the one or more NDR. The size of the central genomic region may be about 1 kb, about 2 kb, about 3 kb, about 4 kb, about 5 kb, about 6 kb, about 7 kb, about 8 kb, about 9 kb or about 10 kb. In one example, a plurality of probes/primers hybridize/bind to an approximately 4 kb region centred at an NDR. The binding sites of a plurality of probes/primers to a central genomic region may be continuous or discontinuous within the central genomic region. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence of the one or more NDR or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence sharing at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98% or at least about 99% sequence identity with the one or more NDR or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence that differs from the one or more NDR or parts thereof by about one, about two, about three, about four or about five nucleotides/bases. In various embodiments, the one or more probe/primer has a sequence that is complementary to a central genomic region or parts thereof related to the one or more NDR. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence sharing at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98% or at least about 99% sequence identity with the central genomic region or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence that differs from the central genomic region or parts thereof or parts thereof by about one, about two, about three, about four or about five nucleotides/bases. In one example, the one or more probe/primer has a sequence that is complementary to an approximately 4 kb region centred at an NDR. A skilled person would be able to determine the suitable conditions that would allow the probe/primer to hybridize to the one or more NDR.

In various embodiments, the one or more NDR comprises one or more NDR of a gene listed in one or more of Table 1, Table 2, Table S3, Table S10, Table S14, Table S15, Table S16, Table S17, Table S18, Table S19, Table S20 and Table S21. In various embodiments, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof. In various embodiments, the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.

In various embodiments, the kit/panel or the probe set/primer set further comprises a probe/primer for detecting a tumor-specific mutation.

In various embodiments, the one or more probe/primer comprises from about 50 to about 200 nucleotides/bases, from about 90 to about 150 nucleotides/bases or from about 110 to about 130 nucleotides/bases. In various embodiments, the one or more probe/primer comprises no more than about 200, no more than about 190, no more than about 180, no more than about 170, no more than about 160, no more than about 150, no more than about 140, no more than about 130 or no more than about 120 nucleotides/bases. In various embodiments, the one or more probe/primer comprises at least about 50, at least about 60, at least about 70, at least about 80, at least about 90, at least about 100, at least about 110 or at least about 120 nucleotides/bases. In various embodiments, the one or more probe/primer comprises about 120 nucleotides/bases.

In various embodiments, the one or more probe/primer comprises the sequence of one or more of SEQ ID NO: 1 to SEQ ID NO: 577 (i.e. SEQ ID NO; 1, SEQ ID NO:2, SEQ ID NO: 3, and so forth till SEQ ID NO: 577, see Supplementary Data 3) or a sequence sharing at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% sequence identity thereto. In various embodiments, the sequence sharing at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99% sequence identity with any one of SEQ ID NO: 1 to SEQ ID NO: 577 is capable of hybridizing/binding to the one or more NDR.

In various embodiments, the kit/panel or the probe set/primer set comprises a plurality of probes/primers.

In various embodiments, the kit/panel/primer set/probe set is for estimating a tumor burden or ctDNA burden associated with cancer, optionally colorectal cancer. In various embodiments, the one or more probe/primer is capable of hybridizing/binding to a genomic region of one or more of the following genes: ARID1A, CCNE1, CDH1, CDK6, CTNNB1, EGFR, ERBB2, KRAS, MUC6, MYC, RHOA, RNF43, SMAD4, TP53 or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a genomic region of one or more of ARID1A, CCNE1, CDH1, CDK6, CTNNB1, EGFR, ERBB2, KRAS, MUC6, MYC, RHOA, RNF43, SMAD4, TP53 or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence sharing at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98% or at least about 99% sequence identity with the genomic region of one or more of ARID1A, CCNE1, CDH1, CDK6, CTNNB1, EGFR, ERBB2, KRAS, MUC6, MYC, RHOA, RNF43, SMAD4, TP53 or parts thereof. In various embodiments, the one or more probe/primer has a sequence that is complementary to a sequence that differs from the genomic region of one or more of ARID1A, CCNE1, CDH1, CDK6, CTNNB1, EGFR, ERBB2, KRAS, MUC6, MYC, RHOA, RNF43, SMAD4, TP53 or parts thereof by about one, about two, about three, about four or about five nucleotides.

In various embodiments, the one or more probes/primers cover at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or about 100% of the target NDR(s)/genomic region(s). In some embodiments, the one or more probes/primers do not overlap each other i.e. the probes/primer are aligned side-by-side when hybridized/bound to the target NDR(s)/genomic region(s). In some embodiments, there is some degree of overlap among adjacent probes/primers (e.g. an overlap of 10 bp, 30 bp, 50 bp, 70 bp, 90 bp etc.).

The number of probes/primers may vary depending on the number of target NDRs/genomic regions, the length/size of the target NDRs/genomic regions and/or the length/size of the probes/primers etc. Higher probe numbers/density may lead to better sampling, although it can also increase the cost of the method. In various embodiments, the number of probes/primers is in the range of from about 25 to about 50, from about 60 to about 80, from about 90 to about 110, from about 125 to about 150, from about 160 to about 180, from about 190 to about 210, from about 225 to about 250, from about 260 to about 280, from about 290 to about 310, from about 325 to about 350, from about 365 to about 390, from about 405 to about 430, from about 445 to about 470, from about 485 to about 510, from about 525 to about 550, or from about 565 to about 590. In various embodiments, the number of probes/primers is at least about 10, at least about 20, at least about 30, at least about 40, at least about 50, at least about 75, at least about 100, at least about 125, at least about 150, at least about 175, at least about 200, at least about 225, at least about 250, at least about 275 or at least about 300. In various embodiments, the number of probes/primers is no more than about 400, no more than about 375, no more than about 350, no more than about 325, no more than about 300, no more than about 275, no more than about 250, no more than about 225 or no more than about 200.

In various embodiments, there is provided a method or a product as described herein.

BRIEF DESCRIPTION OF FIGURES

FIG. 1 Overview of approach. Deep cfDNA WGS profiles of plasma samples from healthy individuals and cancer patients were compared to identify nucleosome depleted regions (NDRs) with tumor/blood tissue-specific expression and differential cfDNA coverage. A model was trained to predict ctDNA levels from NDR cfDNA coverage. A compact assay targeting predictive NDRs was used to perform longitudinal profiling of ctDNA levels and dynamics.

FIG. 2 Characteristics of cfDNA degradation patterns at promoters and exon-intron junctions. (a) Systematic analysis of gene regulatory regions for association of gene expression and cfDNA relative coverage. Relative coverage refers to cfDNA coverage across the given region when normalized to +/−1 kb flanking regions. The nucleosome depleted regions of promoter (NDR, −150 to 50 bp relative to TSS) and first exon-intron junction (NDR, −300 to −100 bp relative to first exon end) are highlighted. (b) Relative cfDNA coverage of promoter and junction NDRs for expressed (fpkm≥30 in whole blood) and unexpressed genes. (c) Distribution of promoter and junction NDR relative coverage for expressed and unexpressed genes.

FIG. 3 Quantitative estimation of colorectal cancer ctDNA burden. (a) cfDNA relative coverage for the promoter region of PPP1R16A (ENST00000528430) overexpressed in CRC tumors relative to whole blood, and cfDNA relative coverage for the junction region of GMFG (ENST00000602185) overexpressed in whole blood relative to CRC tumors. The grey curve shows the mean coverage across CRC samples. (b) Relative coverage score (see Methods) of NDRs in transcripts differentially expressed between CRC tumors and whole blood. (c) Schematic showing how the predictive model of ctDNA fractions was developed: Differentially expressed genes in CRC and blood were identified, NDR relative coverage features were obtained from in silico generated cfDNA samples, predictive features were selected, and a quantitative model was fitted. (d, e) Comparison of expected (in silico simulation) and observed ctDNA fractions across the CRC cfDNA samples in the d) training and e) test set, respectively. The mean absolute error (MAE) is listed for each sample. (f) Comparison between observed and expected ctDNA fractions in the test set.

FIG. 4 Targeted NDR assay to quantify ctDNA burden and monitor cancer progression. (a) Schematic showing how targeted NDR sequencing, low-pass WGS, and targeted gene sequencing was performed on a cohort of 53 CRC plasma samples. (b) Comparison of ctDNA fractions inferred by targeted NDR-sequencing and low-pass WGS (ichorCNA). (c) Comparison of ctDNA fractions inferred by targeted NDR-sequencing and maximum VAFs (maximum VAF of all SNVs identified in a given plasma sample). (d) NDR-quantified ctDNA burden across serial plasma samples and its association with events of cancer progression treatment response. Somatic SNV VAFs are highlighted for each timepoint; SNVs detected in at least two timepoints are shown. SNVs undetected with standard filtering criteria at given timepoints are indicated with a dashed line. Treatment types and intervals are highlighted. Events of disease progression as inferred by computerized tomography (CT) scans are shown.

FIG. 5 Estimation of ctDNA burden across two distinct cancer types. (a) cfDNA relative coverage across the promoter region of the blood-specific gene, RASGRP4 (ENST00000615340). Dark grey and light grey curves show the mean of the coverages from plasma samples from CRC and BRCA patients respectively, respectively. (b) Schematic showing how the ctDNA content prediction model across CRC and BRCA samples was developed. (c, d) Comparison of expected (in silico simulation) and observed ctDNA fractions across CRC and BRCA cfDNA samples in the c) training and d) test set, respectively. The mean absolute error is listed for each sample.

FIG. 6A systematic analysis of gene regions for association of gene expression and cfDNA relative coverage. Relative cfDNA coverage (normalized to +/−1-2 kb regions) for sets of genes grouped by expression level in whole blood cells across a) first, b) second, c) third exon-intron junctions, d) first, e) second, f) third intron-exon junctions, as well as g) promoter, and h) transcript end region.

FIG. 7 Correlation between relative coverage of NDRs and epigenetic features. For each candidate covariate/predictor, a linear regression is fitted with relative coverage as the response. The Pearson correlation coefficient (y axis, signed square root of R-squared from regression) is shown for each candidate variable. Whole blood gene expression (fpkm) is binned into 6 bins [unexpressed, 0.01<fpkm≤0.1, 0.1<fpkm≤1, 1<fpkm≤5, 5<fpkm≤30, fpkm≤>30] and fitted as a categorical covariate with the unexpressed group as the reference group. Peak files of epigenetic features [DNase, H3K4me3, H3K36me3, H3K27ac, H3K4me1, H3K9me3 and H3K27me3] from primary T-cells (E034) were obtained from the Roadmap Epigenomics Project. Epigenetic features are fitted as binary covariates with no signal as the reference group. Barplots of the correlation (r, square root of R2 multiplied by the coefficient sign) between each feature and relative coverage for (a) Promoter NDRs and (b) Junction NDRs are shown.

FIG. 8 Transcripts differentially expressed between CRC tumors and whole-blood. CRC (fpkm_(CRC)>20, fpkm_(blood)<0.1, dark grey) and whole-blood (fpkm_(CRC)<0.1, fpkm_(blood)>10, light grey) specific transcripts are identified from expression data from TCGA and GTEx.

FIG. 9 The evolution of predictive error with model complexity. Mean absolute error between expected and predicted ctDNA fractions of CRC samples is estimated as a function of model complexity (number of predictive features). The error bar size is the standard deviation of MAE values from 231 CRC training samples (light grey).

FIG. 10 Model performance on 10 test sets generated using different (withheld) healthy samples from the training sets. Individual normal samples (n=29) in the healthy cohort were evenly split into 2 sets, used to dilute the plasma samples from CRC patients in training (CRC-1 to 8 in Table S1) and test (CRC-9 to 12) sets separately. (a) The correlation (Pearson and Spearman) between the expected and observed ctDNA fractions across the 10 test sets. (b) The mean absolute error (MAE) between the expected and observed ctDNA fractions for the 10 test sets.

FIG. 11 Comparison of expected and ichorCNA-predicted ctDNA fractions across the CRC cfDNA samples. (a) ctDNA fractions across the CRC cfDNA samples. (b) Comparison of expected and ichorCNA-predicted ctDNA fractions.

FIG. 12 Performance of ichorCNA when applied to the samples with low ctDNA burden. 31 out of 120 low-ctDNA samples of CRC were predicted as non-cancerous by ichorCNA, highlighted in black. Grey dashed line indicates ctDNA fraction of 0.

FIG. 13 Predictive error as a function of model complexity for two distinct cancer types. The error bar size is the standard deviation of MAE values from 446 training samples (light grey).

FIG. 14 Comparison of expected and observed ctDNA fractions in test set across two distinct cancer types.

FIG. 15A BRCA model using BRCA tumor-specific NDRs. (a) The list of top BRCA tumor-specific NDRs that were used for ctDNA content prediction. (b, c) Comparison of expected and observed ctDNA fractions across the BRCA cfDNA samples in the test set.

FIG. 16 Comparison of the ctDNA fractions determined by the CRC model and the “CRC+BRCA” model for the CRC samples in the test set.

FIG. 17 Comparison of the observed ctDNA fractions in the 53 original cfDNA samples with capture-based NDR sequencing (mean coverage ˜300×) and their downsampled counterparts (100×, 50×, 25×, and 10×, respectively).

FIG. 18 Genomic regions over promoters (top) and first exon-intron junction (bottom) used to calculate relative coverage. The mean coverage of the up and downstream 2kbp flanks (grey) is used as a “normalization factor” for the region of interest (black).

FIG. 19 Overview of machine learning feature selection, model fitting, and train/test set performance for colorectal cancer.

FIG. 20 Extensive identification of all predictive CRC features/regions.

FIG. 21 Pan-cancer model training: Overview of Machine Learning feature selection, model fitting, and train/test set performance for pan-cancer features.

FIG. 22 Pan-cancer feature combinations: Extensive identification of all predictive pan-cancer features/regions

FIG. 23 Additional CRC and pan-cancer feature combinations: Extensive identification of all predictive feature combinations using in silico samples generated with random subsets of healthy samples

FIG. 24 The flow chart of establishing a machine learning model based on expression-specific DNA degradation patterns to predict ctDNA fractions for potentially clinical use

FIG. 25 The evolution of the error between observed and calculated ctDNA fractions with the number of top features for CRC prediction model

FIG. 26 The evolution of the error between observed and calculated ctDNA fractions with the number of top features for pan-cancer prediction model

EXAMPLES

Example embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following discussions and if applicable, in conjunction with the figures. It will be appreciated that the example embodiments are illustrative, and that various modifications may be made without deviating from the scope of the invention. Example embodiments are not necessarily mutually exclusive as some may be combined with one or more embodiments to form new exemplary embodiments.

It is shown that the size distribution of cfDNA fragments has a mode of −166 bp, suggesting that nucleosome-bound DNA fragments are protected/preserved during cell death and shed into the circulation. Nucleosome depleted regions (NDRs) are therefore more frequently degraded, yielding a nucleosome-dependent degradation footprint in cfDNA profiles, which can be used to infer tissue of origin. The read depth coverage from sequencing plasma cfDNA is shown to be able to identify nucleosome depletion at a gene's promoter and thus infer gene expression. The coverage of the nucleosome-depleted region at a gene's promoter is negatively correlated with the gene's expression level: a highly expressed gene will tend to have less nucleosome binding across its promoter and therefore lower level of protection and higher levels of DNA degradation. Moreover, plasma cfDNA degradation patterns in cancer patients can be used to infer tumor gene expression.

Here, it is hypothesized that a limited set of tumor or blood-specific NDRs could be used to infer the ctDNA burden (fraction) in the blood circulation of cancer patients. ctDNA burden refers to the relative amount of ctDNA out of all cfDNA molecules in a plasma sample. Using deep cfDNA WGS data from cancer patients and healthy individuals, a quantitative model that infers the ctDNA burden using cfDNA sequencing data from a limited set of NDRs is trained and test. This model is shown to be accurate for plasma samples from both colorectal cancer (CRC) and breast cancer (BRCA) patients (mean absolute error 4.3%), and deployment is explored using a compact targeted sequencing assay for low-cost and quantitative tracking of patient ctDNA dynamics.

The examples demonstrate two components. The first component is a method for estimating ctDNA burden specifically in liquid biopsies from colorectal cancer (CRC) patients. The second component is a method for estimating ctDNA burden in liquid biopsies from any solid tumor (pan-cancer). Both colorectal cancer and pan-cancer models have high prediction accuracy, but the pan-cancer model has the added advantage that it can be applied to any solid tumors.

In one example, the colorectal cancer ctDNA burden estimation model is built as follow. Machine learning was used to develop a predictive model that uses cfDNA coverage patterns at the promoter and junction regions of selected genes to infer ctDNA burden in the blood samples of colorectal cancer patients. The model was trained using data from an in silico “dilution” of 8 samples from 5 cancer patients and healthy individuals, resulting in a training set of 231 “virtual” samples of various ctDNA content (see Table S2). The candidate tumor/blood transcripts that showed both differential expression signal and differential DNA degradation signal at NDRs between CRC tumor and blood were shortlisted. The tumor and blood transcripts were pooled together and their promoter and junction NDR coverage scores were defined as (totally 908) input “features” (see Table S3). The coverage value of each position was normalized by the mean coverage of the upstream (−2000 to −1000 bp) and downstream (+1000 to +2000 bp) regions with respect to transcription start site (for promoter) and exon boundary (for junction) respectively. A Lasso (least absolute shrinkage and selection operator) model was employed to identify features predictive of ctDNA proportions. Half of the training data was extracted randomly to run Lasso (using 1000 repetitions), consequently discovering 6 stable features (probability ≥0.99) from this stability-based exploration (FIG. 19 ). To develop an accurate ctDNA burden estimation model with a minimal sequencing cost, using the 4 to 10 robust features is an optimal solution, because increasing the number of features to over 10 fails in improving the prediction accuracy of test set and thus over-interprets the training set data (see FIG. 25 ) in one example. Here, the top 6 features were employed as an example to train and test the machine learning model.

The model may also be applicable to other cancer types, subtypes, or specific therapeutic settings, considering tissue-of-origin of cfDNA molecules can be principally informed from tissue-specific DNA degradation pattern. Compared with plasma from healthy people, tumor-derived DNA component in cancer plasma samples weakens the blood-specific DNA degradation pattern, which suggests the decay of blood-specific signal might be informative of robustly estimating the ctDNA content regardless of cancer types. Therefore, the ctDNA content estimation method is also extended to the pan-cancer level.

In one example, a pan-cancer ctDNA burden estimation model is built as follows. This pan-cancer model relates to a quantitative method that only uses blood-based features/regions (and no use of tumor type specific regions). First, blood transcripts that are highly expressed in blood and lowly expressed in tumors of all 20 cancer types (BLCA, BRCA, CESC, CRC, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, OV, PAAD, PRAD, SKCM, STAD, THCA, and UCEC) where shortlisted. These yielded 792 promoter and junction NDR candidate coverage features (Table S10). 215 in-silico samples diluted from the plasma samples of 7 breast cancer (BRCA) patients were added into the existing training set of colorectal cancer samples, as well as 93 in-silico samples diluted from the plasma samples of 3 BRCA patients into the existing test set (see Table S2). The same protocol of feature selection and model training that were used for colorectal cancer ctDNA burden estimation above was performed. It was found that using around 10 blood features is able to predict the ctDNA content in plasma samples (see FIG. 26 ). An example of employing 10 stable features (probability≥0.99) (Table 2) that are predictive of ctDNA burden in the training set is shown, with a mean absolute error of ˜2.2% between the calculated and observed ctDNA proportions (FIG. 21 ). The trained model with those 10 features is able to accurately predict the ctDNA content in the test set (MAE of α4.3%). The prediction on breast cancer cases show a promising prediction power of the pan-cancer model.

Based on the guidance provided by this disclosure, users can follow the methodology details to reproduce the work or apply the method to their own data with a full flexibility of tuning the number of features for their model, as long as the selection can achieve high prediction accuracy and prevent data over-interpretation. As described in the examples herein, users can check the error evolution with the number of top features to determine a reasonable range of numbers of features.

Embodiments of a machine learning model based on expression-specific DNA degradation patterns to predict ctDNA fractions for potentially clinical use are described herein (FIG. 24 ). Embodiments of the method enable detection of tumor DNA burden (even of very low frequency) in the blood by only sequencing these selected nucleosome-depleted regions in cfDNA assays. These regions comprise <50 kb (4 kb×6 features or 4 kb×10 features) DNA sequence in total, and may therefore allow for an extremely cost-effective approach to ctDNA content estimation (order of magnitude less DNA sequencing needed compared to standard targeted sequencing assays, usually >1000 kb). Furthermore, embodiments of the assay can be implemented as an extension/add-on to a standard targeted panel assay, allowing for an extremely cost-effective approach to generic ctDNA profiling. The colorectal and pan-cancer models have some key differences. Both colorectal cancer and pan-cancer models have high prediction accuracy, but the pan-cancer model can generalize to most/all solid tumor types (pending validation data in other cancer types).

Results Overview of Approach

Blood samples (n=29) were collected from healthy individuals and plasma cfDNA was extracted for paired-end WGS (merged ˜150× coverage) (FIG. 1 ). Targeted sequencing (see Methods) of plasma samples (CRC n=65, BRCA n=36) from cancer patients was performed and samples (CRC n=12, BRCA n=10) with high SNV VAFs (indicating high ctDNA burden) were selected for deep ˜90× cfDNA WGS (Table S1). In these high ctDNA burden WGS samples, ctDNA burden estimates could be obtained using existing methods (see Methods, Oesper L, Satas G, Raphael BJ. Quantifying tumor heterogeneity in whole-genome and whole-exome sequencing data. Bioinformatics 30, 3532-3540 (2014), Ha G, et al. TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data. Genome research 24, 1881-1893 (2014), Bao L, Pu M, Messer K. AbsCN-seq: a statistical method to estimate tumor purity, ploidy and absolute copy numbers from next-generation sequencing data. Bioinformatics 30, 1056-1063 (2014) and Larson N B, Fridley B L. PurBayes: estimating tumor cellularity and subclonality in next-generation sequencing data. Bioinformatics 29, 1888-1889 (2013)) that infer tumor purity using matched tumor and germline high-depth WGS data. To identify candidate NDR features for the quantitative model, tumor and blood-specific genes with differential NDR cfDNA degradation in their promoters and first exon-intron junctions in plasma samples were identified from healthy individuals and cancer patients. Using a machine learning and in silico cfDNA generation approach, a sparse linear model was trained and tested to predict ctDNA burden from NDR cfDNA coverage. To further explore how the approach could be useful for cost-effective monitoring ctDNA dynamics, a compact (<25 kb) capture-based sequencing assay targeting predictive NDRs was designed to explore the robustness of NDR-based targeted approach using independent plasma samples (n=53) from CRC patients, and applied to estimate ctDNA levels in longitudinally collected plasma samples from a cohort of five colorectal cancer patients.

Association of Gene Expression and cfDNA Fragmentation Patterns

Analysis of cfDNA from the healthy individuals revealed nucleosome depletion and reduced cfDNA protection flanked by a series of strongly positioned nucleosomes at gene promoter regions (FIG. 2 a ). Relative coverage at the promoter NDR was inversely correlated with gene expression in whole blood cells. Studies of nucleosome positioning in cells have found that, apart from promoters, exon-intron junctions are associated with NDRs. The inventors therefore systematically scanned these gene regions for association between gene expression and cfDNA relative coverage (FIG. 2 a ). Strikingly, it was found that the first exon-intron junction of transcripts showed a similar association between coverage and expression, where relative cfDNA coverage at the NDR ranging from −300 to −100 bp with respect to the end of the first exon exhibited a strong inverse correlation with transcript expression in whole blood cells. However, surprisingly, correlation between expression and cfDNA coverage was not observed at other exon-intron and intron-exon junctions as well as at gene ends (FIG. 2 a and FIG. 6 ). As expected, when comparing highly-expressed (fpkm≥30) and unexpressed gene groups, a strong positive correlation (Pearson r=0.81; Spearman correlation, p=0.85) was observed between the cfDNA relative coverage at promoter and first exon-intron junction NDRs across genes (FIG. 2 b ). While relative coverage at these NDRs correlated strongly with gene expression level, relative coverage could not perfectly separate unexpressed from expressed genes (FIG. 2 b, c ), suggesting that additional factors beyond gene expression contribute to NDR cfDNA degradation. To further explore the factors affecting cfDNA degradation at NDRs, the association between NDR relative coverage and a range of epigenetic features was explored (FIG. 7 ). In addition to gene expression levels (linear regression, promoter r=−0.23, junction r=−0.22), relative coverage was negatively correlated with DNase hypersensitivity (promoter r=−0.60, junction r=−0.55), H3K4me3 (promoter r=−0.59, junction r=−0.54), and H3K27ac (promoter r=−0.45, junction r=−0.41), which are markers of open chromatin, active promoters, and active enhancers respectively. In contrast, H3K36me3 (promoter r=0.49, junction r=0.46) and H3K9me3 (promoter r=0.11, junction r=0.10), markers of gene bodies and heterochromatin, were positively correlated with NDR relative coverage.

Cf DNA Coverage Patterns at NDRs in Colorectal Cancer Patients

To further explore the hypothesis that NDR cfDNA coverage in plasma samples from cancer patients is associated with the epigenetic state of tumor cells, a targeted sequencing panel was first used to screen plasma samples from CRC patients for cases of high ctDNA burden (VAF >15% for known cancer driver mutations, FIG. 1 ). 8 plasma samples from 5 patients were initially identified and high-depth WGS was performed on these samples (˜72×-101×, Sample ID: CRC-1 to 8 in Table S1). ctDNA fractions in these samples were inferred using four existing tissue-based estimation methods (see Methods) and the median tumor purity estimate from these methods was used as ctDNA fractions (in the range 35-86%, Table S1). Gene expression data from TCGA and GTEx was then used to identify genes specifically expressed in CRC tumors and whole blood (see methods, FIG. 8 ). As an example, PPP1R16A was identified as a CRC-specific gene with robust depletion of NDR cfDNA coverage in plasma samples from cancer patients as compared to healthy individuals, and GMFG was identified as a blood-specific gene with greater coverage depletion in healthy blood plasma (FIG. 3 a ). As expected, CRC-specific genes generally showed depletion of cfDNA at both promoter and junction NDRs in the plasma of CRC patients compared to healthy controls (FIG. 3 b ). In contrast, blood-specific genes showed higher cfDNA coverage at NDRs in the plasma of CRC patients compared to healthy controls. Furthermore, directly comparing CRC and blood-specific genes, CRC-specific genes had significantly greater cfDNA depletion at NDRs in plasma samples from CRC patients (P<2.2×10⁻¹⁶, Wilcoxon rank-sum test, FIG. 3 b ).

Quantitative Estimation of Colorectal Cancer ctDNA Burden

With the insight that cfDNA coverage at NDRs is associated with the transcriptional state of DNA in the tumor cells, it was hypothesized that cfDNA coverage at a small set of NDRs could be used to infer the ctDNA burden (fraction of tumor DNA out of all cfDNA) in the blood plasma of a cancer patient. As training data, 8 deep WGS samples from 5 CRC patients were in silico “diluted” with data from healthy individuals, resulting in a training set of 231 samples of ctDNA proportions ranging from 0.5% up to the original undiluted fractions (FIG. 3 c , Table S2). Candidate CRC-specific transcripts that were upregulated in CRC tumors (fpkm_(CRC)>10, fpkm_(blood)<1) and had a differential DNA degradation signal at both promoter and junction NDRs (relative coverage score <−0.2) were shortlisted. Candidate blood-specific transcripts were shortlisted with similar criteria (fpkm_(CRC)<1, fpkm_(blood)>10, relative coverage score >0.2). Relative coverages at the NDRs of these candidate transcripts were used as input features (total 529 unique tumor and 379 blood features, Table S3). Lasso L₁-regularization regression was then used in combination with a stability-based feature selection approach to a select a minimal set of 6 predictive NDRs (Table 1), which could predict the ctDNA fraction in the training data with a mean absolute error (MAE) of ˜1.8% (FIG. 3 d ). The signs of coefficients for the 6 NDRs in the trained model corresponded to the sign of differential expression of the associated transcripts in tumor tissue relative to whole blood (Table S4). To evaluate the ability of the model to generalize to unseen data, 4 additional samples (CRC-9 to 12 in Table S1, WGS at ˜80-95×) from 2 new CRC patients were sequenced and an in silico diluted test set of 113 samples was created (Table S2). The model accurately predicted the ctDNA proportion in this independent test set (FIG. 3 e , MAE-3.4%). A direct comparison shows high similarity between the observed (predicted) and expected ctDNA fractions (FIG. 3 f ; Pearson r=0.96; Spearman correlation, p=0.97). To further explore the performance of more complex models, the inventors estimated the predictive error as a function of model complexity (number of top predictive features) and found that models with 4-10 NDR features were generally more accurate and better at generalizing to unseen data compared with models using fewer or more features (FIG. 9 ). Next, the lower limit for ctDNA detection in the NDR model was explored. Using a previous approach (Adalsteinsson V A, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 8, 1324 (2017)), the inventors evaluated the sensitivity and specificity of the model as a function of ctDNA fraction threshold. The 113 in silico test set CRC samples (FIG. 3 e , CRC-9 to 12) were used as positives, and 40 random subsets (Table S5, ˜80× each) from the data of plasma samples (n=29) from healthy individuals were used as negatives. At a 2% ctDNA fraction threshold, the model correctly predicted all positive and negative samples (100% sensitivity and specificity, Table S5). In comparison, at a 1% threshold, the sensitivity was maintained at 100% but the specificity dropped to 75%. FIG. 19 provides an overview of the machine learning feature selection, model fitting, and train/test set performance for colorectal cancer.

To further evaluate the robustness of the model when tested on in silico samples generated using healthy samples not seen during model training, the healthy samples (n=29) were split into two different groups to separately generate in silico training and test data. Reassuringly, this analysis showed robust model performance in the presence of independent train/test healthy samples (FIG. 10 ; test set median Pearson r=0.92; median Spearman correlation, p=0.93; median MAE=5.3%).

Next, the predictive performance of the model was compared with ichorCNA (Adalsteinsson V A, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 8, 1324 (2017)), a method that estimates the ctDNA fraction on the basis of arm-level copy number alterations in low-pass WGS data. Overall, ichorCNA generally predicted comparable estimates of ctDNA burden (FIG. 11 ; Pearson r=0.91; Spearman correlation, p=0.92). However, while 31 out of 120 low burden samples (ctDNA burden <5%) were predicted as non-cancerous by ichorCNA (FIG. 12 ), only 4/120 were predicted as non-cancerous by the NDR approach. This is consistent with the reported 3% lower limit of detection using arm-level CNAs in ichorCNA (Adalsteinsson V A, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 8, 1324 (2017)).

TABLE 1 Table 1 NDR features predictive of ctDNA fraction in CRC. Gene Transcript Chr Site Region Expr. FPKM_(blood) FPKM_(CRC) Pr SHKBP1 ENST00000599716 19 41082891 junction blood 10.66 0.22 1.000 ACSL1 ENST00000454703 4 185747070 junction blood 35.07 0.78 1.000 BCAR1 ENST00000162330 16 75285369 junction tumor 0.00 16.86 1.000 RAB25 ENST00000361084 1 156030951 promoter tumor 0.07 131.50 0.999 PRTN3 ENST00000234347 19 840960 promoter blood 13.78 0.00 0.995 LSR ENST00000605618 19 35739922 promoter tumor 0.22 31.85 0.990 The column Site is the position of the nucleosome-depleted site (GRCh37); Region is the annotated class of the nucleosome-depleted site (promoter or exon-intron junction); Expr. denotes whether the transcript is specifically expressed in CRC tumor tissue or whole blood cells; Pr is the probability/frequency with which the feature was selected in the Lasso stability-selection approach.

Additional Predictive Features for Colorectal Cancer

Apart from the 6 robust features identified, there may exist other predictive features that correlate with ctDNA burden. A step-wise search with Lasso regression on all 344 in silico samples was performed and the top stable 6 features in each step were extracted to estimate ctDNA fractions. The search was repeated for 100 independent times, followed by pooling all predictive features with a deviation threshold of 3% (FIG. 20 ). This analysis yielded 435 6-feature combinations with a predictive accuracy 3% (see Table S14), comprising a total of 158 unique features (see Table S15).

Targeted NDR Assay to Estimate ctDNA Burden

Intriguingly, since the predictive models used data from only a few NDRs, it was hypothesized that a targeted sequencing approach could be deployed for robust and low-cost estimation of ctDNA burden. The CRC model only requires cfDNA relative coverages at 6 NDRs (Table 1). The inventors therefore designed capture probes for these 6 regions (total ˜24 kb) and performed targeted sequencing (˜300×) on 53 new plasma samples from CRC patients (FIG. 4 a ), followed by ctDNA burden estimation from the relative coverage of the NDRs using the existing CRC model. To examine the accuracy of the model on targeted NDR sequencing data, low-pass WGS (˜4×) was also performed on the same plasma samples for ctDNA content estimation with the CNA-based method, ichorCNA. High concordance (Pearson r=0.84; Spearman correlation, p=0.79) of estimated ctDNA burden with the CNA and NDR-based approaches was observed (FIG. 4 b and Table S6). Moreover, in the 53 samples (FIG. 4 a , Table S6), targeted sequencing (˜6000×) of a panel of 100 frequently mutated genes (˜370 kb, Table S7) in colorectal cancer was performed. SNVs called by MuTect and VarScan were intersected and further filtered to minimize false positives (Table S8, see Methods). This analysis identified high-confidence somatic mutations in 27 plasma samples and revealed high correlation (Pearson r=0.85; Spearman correlation, p=0.88) between maximum VAFs and NDR-based ctDNA burden estimates across samples (FIG. 4 c and Table S6). ctDNA was detected in 49 out of 53 (92%) samples with the targeted NDR approach, compared to 33/53 (62%) and 27/53 (51%) with ichorCNA and SNV calling approaches, respectively. The 4 ctDNA-negative samples identified with the NDR approach were also ctDNA-negative using ichorCNA and the SNV approach (Table S6). Overall, this demonstrates that the NDR-based estimation approach is robust and can be deployed with a compact and low-cost targeted sequencing approach.

NDR-Based Monitoring of ctDNA Dynamics and Disease Progression

To further explore how NDR-based ctDNA burden estimation could be used for low-cost monitoring of cancer progression, targeted NDR assay was applied to serial plasma samples collected from five CRC patients (FIG. 4 d ). Overall, targeted NDR profiling showed concordant ctDNA burden dynamics when compared with SNV VAFs profiled in the same samples, with coinciding increases and decreases in ctDNA burden and VAFs over time. For example, patient C357 showed generally increasing ctDNA burden and VAFs over time, and patient C986 had an intermediate coinciding peak in both ctDNA burden and VAFs. Driver mutations in TP53, PIK3CA and APC were detected in patient C986. While VAFs of these mutations were highly correlated, they showed a between-mutation spread of ˜0.1-0.2 VAF units across all timepoints. Similarly, patient C519 had TP53 and APC mutations with a ˜0.2-0.3 unit difference in VAFs. While such differences may be caused by both technical (e.g. capture efficiency) and biological (e.g. clonality or concomitant CNAs) bias, they demonstrate the challenge in estimating ctDNA burden levels based on VAFs alone.

It was noted that a number of plasma samples for which the NDR-based ctDNA burden was inferred to be positive, yet the variant calling pipeline identified no SNVs under default settings. To further understand this discordance, the raw sequencing data in these “mutation-free” plasma samples was manually inspected. Indeed, when searching for variants that were identified in other samples/timepoints from the same patients, the raw sequencing data supported presence of the expected SNVs in all the samples with positive NDR-quantified ctDNA burden (Table S9). In contrast, one plasma sample (patient C1531, day 191) was quantified with zero ctDNA burden by the NDR approach and manual screening confirmed absence of TP53 and APC mutations in this sample (Table S9). Overall, these results highlight the robustness of the targeted NDR assay for ctDNA burden estimation.

It was next explored how ctDNA burden dynamics correlate with response to targeted or cytotoxic treatments. Patient C357 was treated with Regorafenib (days 821-842 after diagnosis) followed Trifluridine (days 979-1026). However, ctDNA burden estimation in this time interval (days 800-1056) showed no drop in ctDNA burden following either treatment, indicating tumor resistance to both drugs; end-treatment CT scans (Day 916 and 1056 respectively) confirmed progressive disease. In contrast, patients with positive response to treatment showed a marked reduction of ctDNA burden in plasma. For example, patient C1531 received the chemotherapy regimen of FOLFOXIRI (days 82-175) and had on and post-treatment CT scans showing partial response. Strikingly, this patient showed a concomitant and marked drop in ctDNA burden both during (day 160) and after (day 191) treatment. In patient C575, TP53 and ATR mutations were only identified at two out of four timepoints by the pipeline. In this patient, both CT scans and ctDNA burden estimation inferred stable disease during the first round of XELOX/bevacizumab treatment (days 612-833). However, during the second round of treatment, both the ctDNA burden increased (day 864) and CT scans confirmed progressive disease, indicating acquired drug resistance. Finally, discrepancies between tumor dynamics inferred from CT imaging and ctDNA burden has previously been reported. Patient C519 reflected one such example, where CT scans indicated progressive disease while both ctDNA burden estimates and mutation VAFs decreased.

Estimation of ctDNA Burden Across Cancer Types

The predictive model for CRC ctDNA burden included 3 (out of 6) NDR coverage features from genes overexpressed in whole blood. Intriguingly, a predictive model completely restricted to blood-specific genes could hypothetically quantify the extent that a cfDNA profile deviates from a healthy baseline profile, allowing prediction of ctDNA burden across different cancer types. Indeed, the inventors were able to identify genes overexpressed in whole blood compared to solid tumor tissue that also had decreased NDR coverage in plasma samples from healthy individuals as compared to patients of distinct cancer types (FIG. 5 a ). To further systematically test this idea, deep (˜72-94×) cfDNA WGS sequencing of blood samples from 10 breast cancer patients was performed (Table S1) and # in silico diluted cfDNA samples of variable ctDNA burden were generated (Table S2, FIG. 5 b ). Since germline data was not available for the BRCA patients, ctDNA fractions were estimated in the 10 BRCA samples using ichorCNA. Transcripts highly overexpressed in whole blood compared to solid tumor tissues were then shortlisted (comprising 20 different solid tumor types, FIG. 5 b ), yielding 792 blood-specific candidate NDR features (Table S10). Using a training dataset comprising cfDNA samples from both CRC and BRCA patients, it was found that models comprising approximately 10 features were able to generalize well to unseen data from both cancer types (FIG. 13 , Table 2).

TABLE 2 Table 2: Pan-cancer top-10 features. Columns/Gene: gene name/Transcript: transcript ID/Chr: chromosome/Site: coordinate of nucleosome-depleted site (GRCh37)/Region: location of nucleosome-depleted site/Group: gene group based on its expression in blood and tumor/FPKM_(blood): FPKM value in normal blood. Their FPKM values in tumors of 20 cancer types (BLCA, BRCA, CESC, CRC, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, OV, PAAD, PRAD, SKCM, STAD, THCA, and UCEC) are all <1. Gene Transcript Chr Site Region Group FPKM_(blood) SLC11A1 ENST00000465984.5 2 219246911 promoter blood 10.54 NLRP12 ENST00000324134.10 19 54327597 promoter blood 9.17 PRTN3 ENST00000234347.9 19 840960 promoter blood 13.78 HMBS ENST00000392841.1 11 118958697 promoter blood 7.28 LILRB3 ENST00000460208.1 19 54721567 promoter blood 51.15 ACSL1 ENST00000513001.5 4 185678973 junction blood 17.65 GP9 ENST00000307395.4 3 128779693 junction blood 9.72 MX2 ENST00000398632.3 21 42774561 promoter blood 7.28 RASGRP4 ENST00000615340.4 19 38916837 promoter blood 6.88 ATG16L2 ENST00000542481.1 11 72534940 promoter blood 25.18

A model fitted with the training data using the top 10 predictive features (Table 2) had a mean absolute error of 2.2%, with comparable accuracy in CRC and BRCA samples (FIG. 5 c ). In the unseen CRC and BRCA test data (FIG. 5 d ), the model achieved an overall accuracy (MAE=4.3%; Pearson r=0.95; Spearman correlation, p=0.97; FIG. 14 ), comparable to the CRC-specific model applied to CRC data (MAE=3.4%; Pearson r=0.96; Spearman correlation, p=0.97; FIG. 3 e, f ) and a BRCA-specific model applied to the BRCA data (MAE=6.1%; Pearson r=0.97; Spearman correlation, p=0.97; FIG. 15 ). A strong concordance was also observed between the CRC+BRCA and CRC-specific models in their predicted ctDNA fractions in the test set plasma samples from CRC patients (Pearson r=0.95; Spearman correlation, p=0.95; FIG. 16 ). The lower limit of detection for the CRC+B RCA model was analysed by evaluating the sensitivity and specificity of the model as a function of ctDNA fraction threshold. The 206 in silico test set samples (113 CRC+93 BRCA, FIG. 5 d ) were used as positives and 40 random subsets (Table S11, ˜80× each) from healthy individuals were used as negatives. At a 3% ctDNA fraction detection limit, the CRC+BRCA model achieved 100% sensitivity and specificity (Table S11). In comparison, at a 2% threshold, the sensitivity was almost maintained at 99.5% but the specificity dropped to 88%. These results support that a model based on a limited set of blood-specific NDR features can predict ctDNA fractions across two distinct cancer types. FIG. 21 provides an overview of the machine learning feature selection, model fitting, and train/test set performance for pan-cancer features.

Additional Predictive Features for Pan-Cancer

Lasso regression with all 792 blood features was employed to identify all potential predictive combination of pan-cancer features. A step-wise extensive search was carried out on all the 652 in silico samples (see Table S2), and the top 10 features in each step were extracted to estimate ctDNA content (FIG. 22 ). The inventors pooled all predictive features with a deviation threshold of 4% from 100 independent runs. This analysis yielded 385 10-feature combinations with a predictive accuracy ≤4% (Table S16), comprising a total of 132 unique features (Table S17).

Additional Predictive Feature Combinations

An additional search for predictive and feature combinations for both the CRC and pan-cancer models was performed. While this search was implemented as previously described (FIGS. 22 and 24 ), a modified approach was used to generate in silico samples, which better preserved variability in cfDNA profiles across individuals: Each cancer cfDNA sample was in silico diluted by the normal data from a random subset (n=19) of all 29 healthy samples. In this analysis, the CRC model yielded 119 new 6-feature combinations with a predictive accuracy ≤4% (FIG. 23 , Table S18), comprising a total of 68 unique features (Table S19). 61 out of these 68 features were also identified as predictive in the previous CRC model (Table S15). Similarly, the pan-cancer model yielded 217 new 10-feature combinations with a predictive accuracy 5% (FIG. 23 , Table S20), comprising a total of 76 unique features (Table S21) with 63/76 identified in the previous pan-cancer model (Table S17).

Discussion

Monitoring of ctDNA offers a non-invasive approach to tracking disease progression and has been demonstrated as a valuable real-time tool for assessing therapeutic response. Here, it is shown that cfDNA coverage patterns at tumor and blood-specific NDRs can be used for quantitative estimation of the ctDNA burden in blood plasma samples. While SNV VAFs can be used as a proxy for the ctDNA burden, this only works for the subset of patients with known and measured clonal SNVs in a given targeted gene panel. SNV-based approximation of ctDNA burden may be further challenged by clonal haematopoiesis, which is frequently observed in cancer patients. Additionally, absolute ctDNA fraction estimation from SNVs requires co-estimation of allele zygosity and clonality, which may be challenging to infer for metastatic patients with multiple independently evolving tumors contributing ctDNA to the blood circulation. Furthermore, in low ctDNA burden samples, which are common and clinically important, NDR-based burden estimation showed improved accuracy as compared to a Ip-WGS-based estimation method. In contrast to Ip-WGS and DNA methylation-based profiling, NDR-based estimation is directly compatible with targeted gene panel sequencing. Since the ctDNA burden estimation model requires data from 10 or less NDRs, these regions can be profiled at low cost by capturing <25 kb of genomic sequence. Targeted cfDNA assays often cover hundreds of genes and >1 Mb captured genomic sequence, with larger panels required for profiling across cancer types and tumour mutation burden estimation. It would be straightforward to co-profile NDRs in such assays, with only a minor increment in panel size. Furthermore, down-sampling analysis showed that the NDR approach is robust down to 100× sequence coverage (FIG. 17 ), imposing a sequencing demand equivalent to ˜0.001×WGS, orders of magnitude lower than current Ip-WGS approaches. Importantly, an integrated NDR/gene assay would be able to estimate ctDNA burden in patients without clonal mutations in targeted cancer genes, potentially corresponding to 5-70% of patients depending on cancer type. The approach could enable low-cost and simultaneous quantitative estimation of ctDNA burden and mutational profiling in response to treatment interventions. Indeed, given the estimated lower limit of detection (˜2%) of the NDR approach, this application (i.e. simultaneous quantitative estimation of ctDNA burden and mutational profiling in response to treatment interventions) may be more relevant as compared to employing the NDR approach for screening of cancer in healthy/cancer-free individuals. Furthermore, critical for treatment decision support, independent ctDNA burden estimates could assist in classification of clonal and subclonal actionable mutations. Intriguingly, it was found that a model restricted to blood-specific NDRs could robustly predict ctDNA burden across both colorectal and breast cancer patients, suggesting it might be possible to estimate ctDNA burden independently of tumor types and metastatic lesions.

Nucleosome positioning across gene bodies, and its association with transcriptional activity, has been studied using both biochemical assays and cfDNA profiles. Unexpectedly, the systematic analysis across ordered exon-intron junctions revealed that, in addition to the promoter, only the first exon-intron junction showed signatures of strong nucleosome and expression-dependent cfDNA degradation (FIG. 2 a and FIG. 6 ). Interestingly, transcription and splicing are coupled processes, and it has been observed that H3K4me3 and H3K9ac chromatin marks of active transcription are concentrated specifically at both promoters and ends of first exons. The data further supports that nucleosome depletion and DNA accessibility at the first exon-intron splice junction is strongly associated with transcriptional activity, supporting a model where the first exon splice region may act as a transcriptional enhancer.

In summary, the inventors have shown how tissue and expression-specific cfDNA degradation at NDRs can be used to quantitatively estimate ctDNA burden in blood samples. The approach is directly compatible with targeted gene sequencing, allowing for low-cost and simultaneous discovery of actionable cancer mutations and accurate estimation of ctDNA burden. It is anticipated that next-generation cfDNA assays based on these findings will be useful for quantitatively tracking and analysing cancer disease progression across time and patients.

Materials and Methods Plasma Samples

Cancer patient and healthy volunteer samples were collected under studies 2013/110/B (now 2018/2795) and 2012/733/B approved by the Singhealth Centralised Institutional Review Board. Plasma was separated from blood within 2 hours of venipuncture via centrifugation at 10 min×300 g and 10 min×9730 g, and then stored at −80° C. DNA was extracted from plasma using the QlAamp Circulating Nucleic Acid Kit following manufacturer's instructions. Sequencing libraries were made using the KAPA HyperPrep kit (Kapa Biosystems, now Roche) following manufacturer's instructions and paired-end sequenced (2×151 bp) on either an Illumina Hiseq4000 or HiseqX.

Whole Genome Sequencing

A targeted sequencing panel (Table S7) was first used to screen plasma samples from CRC patients and 12 samples (Table S1) of likely high ctDNA burden were selected, having maximum VAF >15% for known CRC cancer driver mutations (Supplementary Data 1). Similarly, 10 BRCA plasma samples of high ctDNA burden were selected, with either VAF >15% based on a panel of 77 genes (Table S12) of common breast cancer mutations (Supplementary Data 2), or alternatively, significant proportions (>20%) of short (length <150 bp) cfDNA fragments (Table S1). It has been reported that short cfDNA fragments below 150 bp are enriched in high-ctDNA plasma samples. Deep WGS (˜90×) was performed on the 12 cfDNA samples from 7 CRC patients and 10 cfDNA samples from 10 BRCA patients (Table S1). For the 5 CRC patients with 2 samples each, there was at least a 12 months interval between the two samples. Bwa-mem (Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv preprint arXiv:13033997, (2013)) was used to align the WGS reads from healthy (n=29, ˜5× coverage), cancer (CRC n=12, BRCA n=10, ˜90× coverage), and germline samples (CRC n=12 ˜30× coverage, not available for BRCA) were matched to the hg19 human genome. Duplicates were marked using biobambam (Tischler G, Leonard S. biobambam: tools for read pair collation based algorithms on BAM files. Source Code for Biology and Medicine 9, 13 (2014)). It has been found that trimming reads from both ends increased the coverage signal of nucleosome positioning. Similarly, the original reads (˜151 bp) were trimmed from the two ends and the central 61 bp was preserved to amplify the nucleosome-associated DNA degradation signal. BAM files of healthy individuals were merged using SAMtools merge function (Li H, et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078-2079 (2009)). Low-pass WGS (˜4×) was performed on 53 cfDNA samples from 23 CRC patients (Table S6).

Sample Preparation for Targeted Sequencing

Plasma and patient-matched buffy coat samples were isolated from whole blood within six hours from collection and stored at −80° C. DNA was extracted with the QlAamp Circulating Nucleic Acid Kit, followed by library preparation using the KAPA HyperPrep kit. All libraries were tagged with custom dual indexes containing a random 8-mer unique molecular identifier. Targeted capture was performed on xGen custom panels (Integrated DNA Technologies) relevant to the experiment: a) panel of 100 genes selected based on literature review for relevance to colorectal and breast cancer, see Table S7, or b) capture probes (Supplementary Data 3) targeting genomic regions (4 kb centered at the sites in Table 1) related to the 6 NDRs predictive of ctDNA content in colorectal cancer. Paired-end sequencing (2×151 bp) was done on an Illumina Hiseq4000 machine.

Variant Calling and Allele Frequency Estimation

Sequencing data was analyzed using the bcbio-nextgen pipeline (Guimera R V. bcbio-nextgen: Automated, distributed next-gen sequencing pipeline. EMBnetjournal 17, 30 (2012)), including read alignment with BWA mem, PCR duplicate marking with biobambam, as well as recalibration and realignment with GATK (DePristo M A, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature genetics 43, 491 (2011)). Somatic variant calling was performed using MuTect (Cibulskis K, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nature biotechnology 31, 213 (2013)) and VarScan (Koboldt D C, et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 25, 2283-2285 (2009)) with default parameters, and all calls were annotated with Variant Effect Predictor (McLaren W, et al. The ensembl variant effect predictor. Genome biology 17, 122 (2016)). Variants were removed if they were outside coding regions. The inferred VAFs were either from one of the two callers if the variant was missed by one caller, or the mean if the variant was called by both callers (Table S8). Variants from HLA-A, KMT2C and MUC17 were filtered because the majority of variants in these genes were also found by at least one caller at >=0.005 VAF in buffy coat sequencing.

Gene Expression Analysis

Tissue-specific RNA-seq transcript expression data was obtained from GTEx (including 337 whole blood samples; Table S14). Tumor RNA-seq transcript expression was obtained from TOGA (Table S14). Because a gene usually comprises multiple alternative transcripts with different genomic positions, gene expression was studied at the transcript level for a precise mapping of promoter and junction locations. Transcripts of all coding genes were grouped on the basis of their expression level (fpkm) in whole blood. If a group (e.g. 0.1<fpkm≤1; 25155 transcripts) had more than 5000 transcripts, 5000 transcripts were randomly to represent the group. Unexpressed genes were defined as transcripts that were not expressed in 99% of all 7861 GTEx samples.

Relative Cf DNA Coverage Estimation

Read coverage at promoter and junction regions was computed from BAM files with SAMtools depth function (Li H, et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078-2079 (2009)). For the promoter region (−150 to 50 bp relative to TSS), the mean raw coverage across the region was divided (yielding “relative coverage”) by the mean coverage of the upstream (−2000˜-1000 bp relative to TSS) and downstream (1000˜2000 bp relative to TSS) flanks (FIG. 18 ). Thus, the mean coverage of the combined upstream and downstream 2 k bp flanks serves as a “normalization factor”. A similar approach was used for exon-intron junctions (FIG. 18 ). To measure the difference of relative coverage at NDRs between plasma samples from CRC patients and healthy individuals, the relative coverage score was computed:

${score} = \frac{{{mean}({CRC})} - {mea{n\left( {healthy} \right)}}}{\sqrt{s.d.({CRC})}}$

where mean(CRC) and mean(healthy) are the mean of average relative coverages at NDRs across CRC plasma and healthy plasma samples respectively, and s.d. (CRC) is the standard deviation of average relative coverages at NDRs across CRC samples. The variance in healthy samples could not be estimated due to low sequencing depth (˜5×). When computing average relative coverage of each NDR (either −150 to 50 bp relative to TSS, or −300 to −100 bp relative to first exon end), positions with relative coverage >2 were truncated to reduce bias from potential outlier values.

To explore the association between relative coverage and a range of epigenetic features, linear regression was used to fit each candidate feature (covariate) with relative coverage (response). Whole blood gene expression (fpkm) was discretized into 6 bins [unexpressed, 0.01<fpkm≤0.1, 0.1<fpkm≤1, 1<fpkm≤5, 5<fpkm≤30, fpkm >30] and fitted as a categorical covariate with the unexpressed group as the reference group. Peaks of epigenetic features [DNase, H3K4me3, H3K36me3, H3K27ac, H3K4me1, H3K9me3 and H3K27me3] from primary T-cells (E034) were obtained from the Roadmap Epigenomics Project. Epigenetic features were fitted as binary covariates with no signal as the reference group.

Estimation of ctDNA Fractions from Deep WGS cfDNA Data

The ctDNA fractions in CRC plasma samples were quantified using four different methods: THetA2, TitanCNA, AbsCN-seq and PurBayes (Oesper L, Satas G, Raphael B J. Quantifying tumor heterogeneity in whole-genome and whole-exome sequencing data. Bioinformatics 30, 3532-3540 (2014); Ha G, et al. TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data. Genome research 24, 1881-1893 (2014); Bao L, Pu M, Messer K. AbsCN-seq: a statistical method to estimate tumor purity, ploidy and absolute copy numbers from next-generation sequencing data. Bioinformatics 30, 1056-1063 (2014); Larson N B, Fridley B L. PurBayes: estimating tumor cellularity and subclonality in next-generation sequencing data. Bioinformatics 29, 1888-1889 (2013)). These methods were originally developed to use matched tumor tissue and germline Exome/WGS data to estimate mutation and copy number tumor heterogeneity, including tumor purity. Here, these methods were applied to the ˜90× cfDNA and ˜30× matched germline (buffy coat) WGS data to estimate ctDNA fractions. Somatic mutations and copy number alterations, as input to AbsCN-seq and PurBayes, were called by SMuRF (Huang W, Guo Y A, Muthukumar K, Baruah P, Chang M M, Skanderup A J. SMuRF: Portable and accurate ensemble prediction of somatic mutations. Bioinformatics (Oxford, England), (2019)) and CNVkit (Talevich E, Shain A H, Botton T, Bastian B C. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol 12, e1004873 (2016)), respectively, using the bcbio-nextgen workflow (Guimera R V. bcbio-nextgen: Automated, distributed next-gen sequencing pipeline. EMBnetjoumal 17, 30 (2012)). The median of these four ctDNA fraction estimates for a given sample was used as the final consensus estimate of the ctDNA fraction. Since germline samples were not available for the BRCA patients, the ctDNA fractions of the BRCA plasma samples were estimated by ichorCNA (Adalsteinsson V A, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 8, 1324 (2017)).

In Silico Sample Generation

The cancer cfDNA samples were in silico diluted by mixing cancer cfDNA reads with reads from healthy samples, maintaining the same average coverage as the original undiluted cancer cfDNA sample. The in silico generated samples were diluted from ctDNA content ranging from 0.005 up to the original undiluted fractions, with a denser sampling of low fractions 0.05 (Table S2). The inventors generated a training set of 231 samples originating from 8 samples from 5 CRC patients, and a test set of 113 samples originating from 4 samples from 2 additional CRC patients. For BRCA, the training set comprised 215 in silico generated samples from 7 patients/samples, and the test set had 93 samples from 3 patients/samples (Table S2).

Generation of NDR Features

The relative coverage score (see above) of NDRs for all transcripts was computed and the relative coverage score was combined with expression data to shortlist tumor/blood-specific transcripts associated with differential tumor/blood NDR cfDNA coverage. For each transcript, the inventors calculated its median fpkm (fpkm_(blood)) across all whole blood samples, its median fpkm (fpkm_(CRC)) across all CRC samples, as well as its respective median fpkm values for other tumor types. Tumor transcripts were defined as being highly expressed in CRC tumor, lowly expressed in normal blood cell, and more highly degraded in CRC samples at both promoter and junction NDRs (fpkm_(CRC)>10, fpkm_(blood)<1, relative coverage score <−0.2). Blood transcripts were defined with similar rules (fpkm_(CRC)<1, fpkm_(blood)>10, relative coverage score >0.2). This approach shortlisted 284 CRC and 210 blood transcripts, each transcript with two features (promoter and junction NDR coverage). After removing overlapping features (multiple transcripts sharing the same NDR), NDR coverages of the resulting 529 tumor and 379 blood features (total n=908) were used as input features for predictive modelling. For the CRC+BRCA model, only transcripts with blood-specific expression (fpkm_(blood)>5) that were also lowly expressed (fpkm <1) in tumors of all 20 tumor types were shortlisted (TCGA tumor type acronyms: BLCA, BRCA, CESC, CRC, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, OV, PAAD, PRAD, SKCM, STAD, THCA, UCEC), leading to a total of 792 features.

Lasso Regularized Regression to Predict ctDNA Fraction

Lasso regularized linear regression using glmnet (Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. Journal of statistical software 33, 1 (2010)) was used to select features and predict ctDNA content in plasma cfDNA samples. To select robust features, half of the training data was first extracted randomly and Lasso with ten-fold cross-validation was used to identify features predictive of ctDNA fractions. This procedure was repeated 1000 times and the top stable features (selection frequency 0.99) were extracted as the final predictive features, which resulted in 6 predictive features (Table 1) for the CRC-specific model and 10 predictive features (Table 2) for the CRC+BRCA model, respectively. The inventors trained the final predictive model with ten-fold cross-validation on the full training set. The inventors also attempted to predict ctDNA fractions with log-transformed relative coverage, and tested the performance using a logistic regression model, both of which failed to outperform the current model in prediction accuracy (data not shown).

To evaluate the robustness of the model when was trained and tested on in silico samples generated using independent healthy samples, the normal samples were split evenly into 2 sets. The first set (N1) was used to perform in silico spike-ins/dilution of the training set, and the second set (N2) was used for in silico dilution of the test set. Briefly, the coefficients of the CRC model (comprising the 6 features in Table 1) were re-fitted using the training data (diluted with the N1 healthy samples), and the model accuracy on the withheld test samples (diluted with N2) were then evaluated. This procedure was repeated 10 times and the model accuracy on the test data generated using the independent normal samples was evaluated.

ichorCNA Benchmarking

For the in silico samples, of DNA reads from the 12 deep-WGS CRC samples were mixed with reads from healthy samples to generate in silico low-pass samples (˜0.1×) for ctDNA content estimation using ichorCNA. The usage guidelines with default parameters were followed in the 2 step workflow: 1) read count coverage calculation with HMMcopy Suite, and 2) tumor content estimation with ichorCNA R package.

Data Availability

cfDNA sequencing data have been deposited at the European Genome-phenome Archive (EGA) under the accession code EGAS00001004657. The data is made available for academic research. Data will be released subject to a data transfer agreement.

SUPPLEMENTARY TABLES AND DATA

Table S1. ctDNA burden estimation of plasma samples from cancer patients. Table S2. The in silico samples of various ctDNA content. Table S3. Information on all candidate features of nucleosome-depleted regions for colorectal cancer. Table S4. Coefficients for the selected NDRs in the trained models. Table S5. Observed ctDNA fractions in the LOD analysis for the CRC model. Table S6. CRC plasma samples for Ip-WGS and targeted sequencing. Table S7. A panel of 100 genes frequently mutated in colorectal and breast cancer. Table S8. Variant allele frequency estimation of CRC plasma samples. Table S9. Mutations missed by the callers for the CRC patients with serial plasma samples. Table S10. Information on all candidate pan-cancer features of nucleosome-depleted regions. Table S11. Observed ctDNA fractions in the LOD analysis for the CRC+BRCA model. Table S12. A panel of 77 genes for screening breast cancer samples. Table S13. Transcript expression data. Table S14. Information on all predictive features for colorectal cancer Table S15. Information on predictive features for colorectal cancer Table S16. Information on additional predictive pan-cancer features Table S17. Information on predictive pan-cancer features Table S18. All predictive feature combinations for CRC using in silico samples generated with random subsets of healthy samples. Table S19. Information on predictive features for CRC using in silico samples generated with random subsets of healthy samples. Table S20. All predictive pan-cancer feature combinations using in silico samples generated with random subsets of healthy samples. Table S21. Information on predictive pan-cancer features using in silico samples generated with random subsets of healthy samples.

Supplementary Data 1 Supplementary Data 2 Supplementary Data 3

TABLE S1 ctDNA burden estimation of plasma samples from cancer patients. tumor content estimation - tumor content estimation - sample cancer repetition 1 repetition 2 sample name ID type coverage theta2 titanCNA abscnseq PurBayes theta2 titanCNA 1014_180816 CRC-1 CRC 80.84 0.38 0.55 0.48 0.43 0.38 0.55 1279_221015 CRC-9 CRC 94.67 0.43 0.65 0.50 NA 0.43 0.65 1279_241116 CRC-10 CRC 95.22 0.66 0.49 NA 0.40 0.66 0.49 1531_160616 CRC-2 CRC 90.65 0.86 NA NA 0.93 0.86 0.82 1531_180119 CRC-3 CRC 100.63 0.67 0.48 0.32 0.30 0.75 0.48 512_051015 CRC-11 CRC 79.96 0.64 0.69 0.49 0.44 0.64 0.69 512_130114 CRC-12 CRC 79.90 0.27 0.51 0.44 0.35 0.27 0.51 519_210114 CRC-4 CRC 87.27 0.30 0.40 0.35 0.36 0.30 0.40 809_030915 CRC-5 CRC 75.76 0.45 0.64 0.59 0.44 0.45 0.64 809_110914 CRC-6 CRC 72.56 0.35 0.59 NA NA 0.35 0.59 986_100215 CRC-7 CRC 71.63 0.25 0.69 0.50 0.36 0.25 0.69 986_261016 CRC-8 CRC 76.72 0.34 0.54 0.51 0.37 0.34 0.54 tumor content estimation - tumor content estimation - mean median repetition 2 repetition 3 ctDNA ctDNA sample name abscnseq PurBayes theta2 titanCNA abscnseq PurBayes content content 1014_180816 0.48 0.43 0.38 0.55 0.48 0.43 0.46 0.45 1279_221015 0.50 NA 0.43 0.63 0.50 0.83 0.56 0.50 1279_241116 NA 0.40 0.66 0.49 NA 0.40 0.52 0.49 1531_160616 NA 0.94 0.85 0.81 NA 0.93 0.87 0.86 1531_180119 0.32 0.83 0.75 0.50 0.32 0.79 0.54 0.49 512_051015 0.49 0.44 0.59 0.68 0.49 0.88 0.60 0.61 512_130114 0.44 0.35 0.27 0.52 0.56 0.35 0.40 0.39 519_210114 0.35 0.36 0.30 0.43 0.35 0.35 0.35 0.35 809_030915 0.59 6.44 0.45 0.63 0.59 0.94 0.57 0.59 809_110914 NA NA 0.35 0.60 NA 0.47 0.47 0.47 986_100215 0.50 0.36 0.25 0.47 0.50 0.37 0.43 0.42 986_261016 0.51 0.37 0.34 0.54 0.51 0.37 0.44 0.44 sample name sample ID cancer type coverage ctDNA content estimated from ichorCNA D14 BRCA-1 BRCA 86.98 0.70 D23 BRCA-2 BRCA 79.41 0.76 D7 BRCA-3 BRCA 94.33 0.13 D9 BRCA-4 BRCA 89.86 0.66 E10c BRCA-5 BRCA 87.92 0.58 E7c BRCA-6 BRCA 85.45 0.51 E8c BRCA-7 BRCA 78.51 0.54 D19 BRCA-8 BRCA 76.67 0.74 E2c BRCA-9 BRCA 71.80 0.41 E62 BRCA-10 BRCA 71.50 0.54

TABLE S2 The in silica samples of various ctDNA content. 4 posient D sample name sample D MNA fraction sample size training set 1014 1014,180816 CRC-1 0.005, 0,010, 0,015, 0,020, 0,025, 0,030, 0,035, 0,040, 0,045, 0.050, 0.075.0.100, 0.125.0,150.0.175, 0.200, 27 0,225. 0.250, 0.275, 0.300, 0.325, 0.350, 0.375, 0.400, 0.425, 0.450, 0.455 CRC 1531 1531160616 CRC2 0,005. 0.010.0.018, 0.020,0.0250.020,0.035,0.040,SMS, 0.050,0,075,0,100,5.125,0.150,0.1 IS.0.200. 43 0.225, 0.250,0.275, 0.300,0.325,0.350.0.375.0.4000.425.0.475,0.500,0.525,0,550,S.575.0.800, 0.625, 0,660,0.675,0,700,0.725,0.750,0.775,0.800,0.825, 0.850,0.858 1531 1531,180119 CRO3 0.005.0,015, 0,020, 0,025, 0,030, 0,035, 0,040, 0,045, 0.090, 0.075.0.100.0.125.0.150.0.175. 0,200, 28 0.225. 0.250 0.275, 0.300, 0,325, 0.350,0.375, 0.400, 0.425, 0.450,0.475, 0.490 519 $19,210114 CRO-4 0.005, 0.010, 0.015,0.020, 0.025, 0.030, 0.035, &M0, SMS, 0.050, 0.075,0,100, 0.125,0.150,0.17S. 0.200, 23 0.225, 5.250,0.275, 6.300,0.325, 0.350. 0.351 809 309,030915 CRC5 0.005, SMS, SMS, 0.020, 0.025, 0.030.0.035.0.040 SMS. 0,050. 0.075. 0.100, 0.125.. 0.150.0.175, 0.200. 32 0.225. 0 250,0 275,0.300), 0.325, 0.350, 0.375, S.400,0.425,0.450,0.475,0.500,0.525, 0.550. 0.575. 0.580 809 809110914 CRC6 0.005. SMS, 0 615,0,020, 0.025, 0,030 SMS. 0.040, SMS. 0.050, 0.075.0.180.0.125. 0.150. 0175. 0 200, 27 0.225, 0.258,0.275,0.300, 0.325, 0 350,0.375, 0,400,0.425, 8.450,0.469 986 988,,100215 CR07 SMS. SMS. SMS. 0.020,0.025 0,030.0.035. 0.040, SMS, 0.050, 0,075, 8.100,8.125.0,150, 0.1 IS. 0.200, 25 0.226, 0.250, 0.275, 0.300,0,325, 0,350, 0.375, 0400. SMS 988 986,261016 CRC-8 0005, SMS, SMS, 0,020,0.025, 0,030. 6,035. QMS. QMS. 0.050, 0.075, 0 100, 0.125, 8,158,0.175, 0.200, 26 0.225. 8 250, 8275,0.300, 0.325, 0.350, 0.375, 0.408.0.42$, 0.448 traising set BRCA-D14 DU BRCA- QMS. QMS. QMS. 0.020, 0.025, 0.030, SMS. SMS, SMS, 0.080, 0.075, 0.100, 0.125, 0.150. 0.1 IS. 0.200 36 0.225, 0.258,0.275,0.300. 0.325, 0.350, 8.375.0.400, S 425, SASS, 0.475, 0,500, 8.525,8.558,0.575 0.600, 0625, QMS, 0.875,0.6967 BRCA BRCA-023 023 BRCA.2 0005, QMS, QMS, 0.020, 0.025, 0,030.0.835. QMS. QMS. 0.050, 0,075.8.183,0.125, 0.150, 0.1 75, QMS, 39 0.225.0,250, 0.275, 8.300,0,325, 8.350,0.375, 0,400, 0.425.0.450, 0.475, 0.500. 0.525.0.550. 0,575.0,600, 0.625, 0.658,0.675,0.700. 0.725, 0.750, 0,7567 BRCA-O7 07 BRCA-3 0,005. 0.010. SMS. 0.020, 0.025 0.030, 0,035, SMS, QMS, 0.050, 0.075,8,180.3.125.9,1288 14 BRCA-09 09 8RCA4 0.005. SQM, SMS, 0.020, 0.025, SMS, SMS. QMS, QMS, 0.058,0.375.0.100 0.125.8.150. 0.175 Q.2M, 35 0.225. 0.258.0.275,0.300. 0.325. 0.350, 0,375.0.400, 0.425, CAMS, 0.475,8,500,8.526,6.668.0.57S. 0.600, 0.626, 0,850,0.6577 BRCA-E1Qc E1c BRCA-5 QMS, QMS, SMS, 0,020, 0.025, 8.030,6.035.0.040. QMS. 0.050, 0.075, 0.100, 0.125, 8.150,0.175, 0.200, 32 0.225. 6 250, 8 275.0.300, 0.325, 0.350, 0.375, 0.408,0.42$, 0.480,0.475,0.500, 0.525.0.550. 0.575 0.5831 8RCA-E7c El BRCA-8 0.005. 0.010, SM5.0.020, 0.025, 0.0230, SMS, QMS, QMS, 0.990, 0.075, 0.18-0,0.12S. 0.150 3.178.3.2®. 39 QMS. 0.268,0.275.0.300, 0325,0.350, 8375, 0,400, 0,425, 0,450, 0,475, 8.500,0.5076 BRCA/ES EB BRCA-T 000 QMS.SMS, 0.020,0.025, 0.030, 0.835. QMQ. SMS>, 0,050, 0.075, 0,100, 8.125,0.158, 0.175,0.200, 36 0.225. 6250,0.275, 0,300, 0,325, 0.350,0.375, 0.408.0.425. 0.450,0.475.0.600. 0,525.8,5356 Table S2 (continued) test set CRC 1279 1279,221015 ORQ-9 9,005,0.010, 0.015, 0.020, 0.025, 0.030, 0.036, 0.040, 0.045, 0.050. 0.075, 0.100, 0.125. 9.150, 0.176,0.200. 28 0.225, 0.250, 0.275, 0.300, 0.325,. 0.350. 0.375, 0.400, 0.425. 0,450, 0.475.0.500 1279 1279,241118 CRO-10 0,005, 0.010, 0.015, 0.020, 0.025. 0.030, 0.035, 0.040, 0.045, 0.050, 0.075, 0.100, 0.125, 0.150, 0.175, 0.200, 28 0.225, 0.250, 0.375,0.300, 0.325,0.350. 0.375,0,400, 0.425, 0,460, 0.475,0.490 512 512,051015 CRO-11 0.006, 0.010, 0.016, 0.020, 0,025, 0.030, 0.035, 0,040, 0.945, 0,050, 0.075,0.100, 0,125, 0,150. 0.1 75, 0,200, 33 0.225, 0.250. 0.275,0.300, 0.325. 0.350, 0.378. 0.400, 0.425, 0.-150.0.475, 0.500, 0.525. 0.550, 0.575,0.600,0.814 512 512 130114 CRC-12 0.005. 0,010, 0.01 5.0.020,0.025, 0030, 0.035,0.040, 0.045,0.050. 0.075, 0.100.0,125, 0.150,0,175.0.200, 24 0.225, 0.250, 0.275,0.300, 0.325,0.350, 0.375, 0.394 tests®! 019 019 BRCA-8 0.005, 0.010,0.015, 0.020,0.025, 0.030, 0.035,0.040, 0.045, 0,050, 0.075, 0.100,0.125, 0,150,0.175,0.200, 38 } 0.225, 0.250,0,275, am 0.325,0.350. am 0.400,0,425, 0.450,0.475, am 0.525,0,550, 0.575, 0,800, 0.825, 0,650, 0.575, 0.700, 0.725, 0.7:303 BRCA E2 E2 BRCA9 0.005.0.010, 0.015.9.020.0.025, 0.030.0.635,0.040, 0.045. 0.050, 0.075.0.100. 0.125, 0.150.0.175.0.200, 25 0.225, 0,250. 0.275, 0.300, am 0.350, 0.375.0.400, 0.4122 Ekc EB BRCA-10 0.005, 0.010, 0.01 5,0.020, 0.025, 0.030, DM 0.040,0.045, 0.050, 0.076, 0.100, 0.125,0.150. 0.175, 0.200, 30 6.225,0.250. 0.275, am 0.325. am am am 0,425, am 0.475, am 0.525, 0.5386

TABLE S3 Information on all candidate features of nucleosome-depleted regions for colorectal cancer. ID Transcript Gene Chr Site Region Group FPKM_(blood) FPKM_(tumor) 1 ENST00000003084.10 CFTR 7 117120017 promoter tumor 0.00 30.20 2 ENST00000027335.7 CDH17 8 95220815 promoter tumor 0.00 149.83 3 ENST00000161006.7 PRSS22 16 2908171 promoter tumor 0.00 10.29 4 ENST00000162330.9 BCAR1 16 75285507 promoter tumor 0.00 16.86 5 ENST00000201586.6 SULT2B1 19 49055332 promoter tumor 0.03 16.67 6 ENST00000211314.4 TMEM14A 6 52535907 promoter tumor 0.67 25.17 7 ENST00000215582.7 MISP 19 751126 promoter tumor 0.00 116.54 8 ENST00000215743.7 MMP11 22 24115006 promoter tumor 0.08 42.41 9 ENST00000216968.4 PROCR 20 33759876 promoter tumor 0.36 28.48 10 ENST00000221992.10 CEACAM5 19 42212537 promoter tumor 0.00 1235.90 11 ENST00000223271.7 RARRES2 7 150038763 promoter tumor 0.41 46.30 12 ENST00000226230.7 TMEM97 17 26646121 promoter tumor 0.39 20.84 13 ENST00000226760.5 WFS1 4 6271577 promoter tumor 0.35 15.01 14 ENST00000227868.8 PDHX 11 34938119 promoter tumor 0.99 13.52 15 ENST00000228916.6 SCNN1A 12 6484715 promoter tumor 0.05 32.36 16 ENST00000230588.8 MEP1A 6 46761127 promoter tumor 0.00 21.95 17 ENST00000232458.9 ECT2 3 172468472 promoter tumor 0.28 12.07 18 ENST00000245451.8 BMP4 14 54423529 promoter tumor 0.00 16.43 19 ENST00000245907.10 C3 19 6720693 promoter tumor 0.37 15.08 20 ENST00000250405.9 BCL2L2 14 23775971 promoter tumor 1.00 11.63 21 ENST00000254260.7 RHPN2 19 33555794 promoter tumor 0.03 23.49 22 ENST00000255681.6 MACROD1 11 63933533 promoter tumor 0.54 22.18 23 ENST00000256585.9 REG4 1 120354283 promoter tumor 0.09 37.82 24 ENST00000256951.9 EMP1 12 13349650 promoter tumor 0.39 14.17 25 ENST00000260227.4 MMP7 11 102401484 promoter tumor 0.00 29.38 26 ENST00000261769.9 CDH1 16 68771128 promoter tumor 0.00 123.30 27 ENST00000262429.8 ATP2C2 16 84402133 promoter tumor 0.34 16.47 28 ENST00000262753.8 POF1B X 84634748 promoter tumor 0.02 40.41 29 ENST00000263629.8 MTIF2 2 55496384 promoter tumor 0.85 13.76 30 ENST00000263735.8 EPCAM 2 47596287 promoter tumor 0.11 594.54 31 ENST00000263895.8 RND3 2 151344208 promoter tumor 0.00 10.29 32 ENST00000264144.4 LAMC2 1 183155423 promoter tumor 0.01 31.46 33 ENST00000264748.6 FGFRL1 4 1006239 promoter tumor 0.82 17.03 34 ENST00000266980.8 SLC39A5 12 56624436 promoter tumor 0.00 20.87 35 ENST00000267101.7 ERBB3 12 56473645 promoter tumor 0.00 40.98 36 ENST00000267814.13 SORD 15 45315302 promoter tumor 0.93 13.70 37 ENST00000267996.11 TPM1 15 63334957 promoter tumor 0.87 32.98 38 ENST00000269571.9 ERBB2 17 37856333 promoter tumor 0.00 11.47 39 ENST00000270560.3 TM4SF5 17 4675187 promoter tumor 0.00 18.39 40 ENST00000271064.11 TINAGL1 1 32042136 promoter tumor 0.10 42.75 41 ENST00000278559.7 CAPN5 11 76777988 promoter tumor 0.52 27.31 42 ENST00000278937.6 MPZL2 11 118134997 promoter tumor 0.37 17.05 43 ENST00000288937.6 MRPL17 11 6704632 promoter tumor 0.85 16.44 44 ENST00000290130.3 MIS18A 21 33651380 promoter tumor 0.49 12.76 45 ENST00000290913.7 CHCHD6 3 126423063 promoter tumor 0.65 15.07 46 ENST00000291525.11 TFF3 21 43735463 promoter tumor 0.00 209.02 47 ENST00000292401.8 AZGP1 7 99573780 promoter tumor 0.14 45.24 48 ENST00000292408.8 FGFR4 5 176513887 promoter tumor 0.07 25.86 49 ENST00000295092.2 FAM84A 2 14772810 promoter tumor 0.00 13.18 50 ENST00000296129.5 CDCP1 3 45187914 promoter tumor 0.11 15.27 51 ENST00000296252.8 LIPH 3 185270401 promoter tumor 0.03 12.23 52 ENST00000296424.8 BDH2 4 104021040 promoter tumor 0.99 14.16 53 ENST00000296666.12 PRRC1 5 126853301 promoter tumor 0.95 11.62 54 ENST00000297205.6 STEAP1 7 89783689 promoter tumor 0.00 14.91 55 ENST00000299610.4 MFAP4 17 19290553 promoter tumor 0.39 15.19 56 ENST00000299714.7 SEC11C 18 56807107 promoter tumor 0.62 11.38 57 ENST00000300119.7 MYO1A 12 57443901 promoter tumor 0.00 15.11 58 ENST00000300283.10 CKMT1B 15 43885252 promoter tumor 0.00 35.88 59 ENST00000300557.2 PRR15L 17 46035244 promoter tumor 0.03 96.21 60 ENST00000301395.7 GGT6 17 4463876 promoter tumor 0.00 16.81 61 ENST00000301887.8 BATF2 11 64764517 promoter tumor 0.43 11.12 62 ENST00000307078.9 AXIN2 17 63557765 promoter tumor 0.09 14.10 63 ENST00000308302.3 GOLT1A 1 204183220 promoter tumor 0.03 12.22 64 ENST00000308831.6 RHOD 11 66824289 promoter tumor 0.07 10.41 65 ENST00000310398.6 AGR3 7 16921611 promoter tumor 0.00 33.08 66 ENST00000310706.9 JUP 17 39942950 promoter tumor 0.87 86.21 67 ENST00000310836.10 UGT8 4 115519611 promoter tumor 0.04 14.08 68 ENST00000311160.13 TNS3 7 47621742 promoter tumor 0.68 16.18 69 ENST00000311381.7 C6orf203 6 107349417 promoter tumor 0.93 14.55 70 ENST00000311620.6 ANKS4B 16 21244986 promoter tumor 0.00 10.61 71 ENST00000316673.8 HNF4A 20 42984340 promoter tumor 0.00 10.78 72 ENST00000317508.10 PRSS8 16 31147083 promoter tumor 0.11 143.22 73 ENST00000318024.8 USH1C 11 17565963 promoter tumor 0.00 46.62 74 ENST00000318407.4 BOK 2 242498136 promoter tumor 0.57 13.75 75 ENST00000318443.9 CD276 15 73976554 promoter tumor 0.00 11.45 76 ENST00000318683.6 B3GNT3 19 17905919 promoter tumor 0.00 57.75 77 ENST00000319838.9 GPR35 2 241544848 promoter tumor 0.31 30.59 78 ENST00000322536.7 DDX10 11 108535752 promoter tumor 0.75 10.84 79 ENST00000324038.6 FAM101A 12 124773710 promoter tumor 0.00 10.08 80 ENST00000325307.11 HMGB3 X 150151759 promoter tumor 0.30 14.09 81 ENST00000325568.9 IL32 16 3115298 promoter tumor 0.93 14.52 82 ENST00000326587.11 MAGED1 X 51636698 promoter tumor 0.60 16.14 83 ENST00000329875.12 PYCR1 17 79894755 promoter tumor 0.12 36.33 84 ENST00000331243.4 FAM84A 2 14772824 promoter tumor 0.01 33.07 85 ENST00000331595.8 BGN X 152760397 promoter tumor 0.60 74.92 86 ENST00000332149.9 TMPRSS2 21 42880086 promoter tumor 0.02 43.57 87 ENST00000333090.4 TSKU 11 76494283 promoter tumor 0.00 17.21 88 ENST00000334047.11 F3 1 95007356 promoter tumor 0.08 13.07 89 ENST00000334869.8 LGMN 14 93215047 promoter tumor 0.94 45.73 90 ENST00000337682.8 FAM60A 12 31479306 promoter tumor 0.97 25.73 91 ENST00000338660.5 VWA1 1 1370903 promoter tumor 0.06 21.82 92 ENST00000339276.5 SFN 1 27189629 promoter tumor 0.60 113.82 93 ENST00000340556.10 MORN2 2 39103103 promoter tumor 0.33 11.41 94 ENST00000344616.3 S100A14 1 153588808 promoter tumor 0.00 143.55 95 ENST00000350051.7 BIRC5 17 76210279 promoter tumor 0.63 18.32 96 ENST00000352551.9 UBE2C 20 44441313 promoter tumor 0.00 10.99 97 ENST00000354624.5 HKDC1 10 70980059 promoter tumor 0.14 20.07 98 ENST00000354900.7 LSR 19 35739675 promoter tumor 0.75 31.22 99 ENST00000355097.6 ENTPD2 9 139948497 promoter tumor 0.03 10.14 100 ENST00000355808.9 PDHA1 X 19362068 promoter tumor 0.25 16.21 101 ENST00000355899.7 PLS3 X 114795509 promoter tumor 0.00 12.05 102 ENST00000356509.7 GMNN 6 24775159 promoter tumor 0.57 11.97 103 ENST00000356762.7 CRB3 19 6464294 promoter tumor 0.00 12.29 104 ENST00000357166.10 ZDHHC9 X 128977860 promoter tumor 0.29 20.11 105 ENST00000357602.7 IPO5 13 98612503 promoter tumor 0.80 15.40 106 ENST00000358278.7 TPM1 15 63334884 promoter tumor 0.43 69.53 107 ENST00000358432.7 EPHA2 1 16482582 promoter tumor 0.03 23.85 108 ENST00000358813.4 CCL20 2 228678570 promoter tumor 0.00 33.26 109 ENST00000358867.10 TMEM126B 11 85339629 promoter tumor 0.47 17.68 110 ENST00000360325.11 CLDN7 17 7165797 promoter tumor 0.09 133.65 111 ENST00000360605.8 URI1 19 30414551 promoter tumor 0.44 12.86 112 ENST00000360760.9 SPATS2L 2 201171247 promoter tumor 0.73 32.04 113 ENST00000360779.3 SDCBP2 20 1309883 promoter tumor 0.00 17.84 114 ENST00000360798.7 LSR 19 35739668 promoter tumor 0.30 55.63 115 ENST00000361084.9 RAB25 1 156030951 promoter tumor 0.07 131.50 116 ENST00000361852.8 EPS8L3 1 110306546 promoter tumor 0.00 26.64 117 ENST00000361901.6 CALD1 7 134464429 promoter tumor 0.42 33.93 118 ENST00000366787.7 THBS2 6 169654139 promoter tumor 0.07 14.23 119 ENST00000366999.8 NEK2 1 211848960 promoter tumor 0.16 11.93 120 ENST00000367274.8 UBE2T 1 202311108 promoter tumor 0.63 29.13 121 ENST00000367283.7 ELF3 1 201979715 promoter tumor 0.07 135.46 122 ENST00000367284.9 ELF3 1 201979645 promoter tumor 0.02 50.55 123 ENST00000367313.4 LAD1 1 201368676 promoter tumor 0.05 100.09 124 ENST00000367976.3 CTGF 6 132272513 promoter tumor 0.32 44.18 125 ENST00000368408.3 EFNA3 1 155051348 promoter tumor 0.36 18.08 126 ENST00000368554.8 PRAP1 10 135122914 promoter tumor 0.00 32.41 127 ENST00000369406.7 HMGCS2 1 120311517 promoter tumor 0.00 17.63 128 ENST00000370481.8 GBP3 1 89488565 promoter tumor 0.66 12.56 129 ENST00000370828.3 GPC4 X 132549518 promoter tumor 0.03 13.27 130 ENST00000371221.3 ALDH18A1 10 97416463 promoter tumor 0.04 29.55 131 ENST00000372486.5 NTMT1 9 132371163 promoter tumor 0.00 14.12 132 ENST00000372966.7 NOX1 X 100129334 promoter tumor 0.00 48.52 133 ENST00000373255.8 H2AFY2 10 71812552 promoter tumor 0.42 12.60 134 ENST00000373290.6 TSPAN15 10 71211229 promoter tumor 0.30 60.96 135 ENST00000373669.6 PIN4 X 71401529 promoter tumor 0.87 13.81 136 ENST00000373699.5 PPIL1 6 36842800 promoter tumor 0.85 17.26 137 ENST00000373944.7 ZWINT 10 58121036 promoter tumor 0.38 16.27 138 ENST00000374183.4 BSPRY 9 116111821 promoter tumor 0.22 15.59 139 ENST00000374214.3 UQCC2 6 33679504 promoter tumor 1.00 17.77 140 ENST00000374837.7 MAP1LC3A 20 33134658 promoter tumor 0.87 16.45 141 ENST00000375431.8 GRTP1 13 114018441 promoter tumor 0.05 18.16 142 ENST00000376569.7 DDR1 6 30851846 promoter tumor 0.08 11.00 143 ENST00000376652.8 ENTPD6 20 25176356 promoter tumor 0.44 14.06 144 ENST00000378115.2 ARHGEF35 7 143892748 promoter tumor 0.10 13.16 145 ENST00000378378.8 ARHGEF16 1 3370990 promoter tumor 0.00 12.12 146 ENST00000378427.5 FAM213B 1 2518237 promoter tumor 0.59 12.06 147 ENST00000379046.6 NQO1 16 69760487 promoter tumor 0.07 39.35 148 ENST00000379047.7 NQO1 16 69760571 promoter tumor 0.09 34.23 149 ENST00000379715.9 EEF1E1 6 8102811 promoter tumor 0.59 17.82 150 ENST00000379742.4 POSTN 13 38172895 promoter tumor 0.01 11.69 151 ENST00000379805.3 PDHA1 X 19362086 promoter tumor 0.76 11.58 152 ENST00000379923.5 ACO1 9 32384618 promoter 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ENST00000494801.5 TCEAL4 X 102840491 promoter tumor 0.60 13.59 214 ENST00000495558.1 VWA1 1 1370241 promoter tumor 0.00 13.92 215 ENST00000495848.1 ELF3 1 201979722 promoter tumor 0.00 17.88 216 ENST00000496195.1 GLRX3 10 131977638 promoter tumor 0.98 10.30 217 ENST00000497734.5 SRC 20 35973088 promoter tumor 0.00 12.44 218 ENST00000507614.1 TIMM8B 11 111957446 promoter tumor 0.80 10.54 219 ENST00000507699.1 PALLD 4 169819128 promoter tumor 0.31 14.56 220 ENST00000514985.5 SEPP1 5 42812181 promoter tumor 0.59 49.95 221 ENST00000520271.5 COX6C 8 100905850 promoter tumor 0.51 12.86 222 ENST00000523677.5 C1orf210 1 43751250 promoter tumor 0.00 13.49 223 ENST00000524832.5 CHID1 11 902322 promoter tumor 0.42 10.82 224 ENST00000525657.1 C1QTNF5 11 119211508 promoter tumor 0.05 17.27 225 ENST00000526202.5 LMO7 13 76334795 promoter tumor 0.09 23.11 226 ENST00000527020.5 USH1C 11 17565947 promoter tumor 0.00 10.90 227 ENST00000527106.5 FUT6 19 5838771 promoter tumor 0.00 13.22 228 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424 ENST00000528780.5 IFITM1 11 313506 promoter blood 47.88 0.31 425 ENST00000529635.5 TBC1D10C 11 67171600 promoter blood 16.89 0.34 426 ENST00000533968.1 SPI1 11 47400038 promoter blood 12.90 0.22 427 ENST00000534862.5 HCK 20 30639991 promoter blood 16.31 0.23 428 ENST00000535669.6 CD37 19 49838684 promoter blood 33.70 0.19 429 ENST00000539932.5 SLC11A1 2 219246926 promoter blood 50.32 0.02 430 ENST00000540998.5 CDC42SE1 1 151032125 promoter blood 10.52 0.00 431 ENST00000542481.1 ATG16L2 11 72534940 promoter blood 25.18 0.37 432 ENST00000542590.1 TBC1D10C 11 67171660 promoter blood 43.95 0.92 433 ENST00000543576.5 DENND1C 19 6481798 promoter blood 12.06 0.00 434 ENST00000544232.5 TMEM91 19 41882645 promoter blood 12.57 0.20 435 ENST00000544665.7 ITGAM 16 31271315 promoter blood 56.38 0.99 436 ENST00000546704.1 ARHGAP9 12 57868923 promoter blood 19.20 0.13 437 ENST00000550399.5 ARHGAP9 12 57868717 promoter blood 14.44 0.45 438 ENST00000552370.5 TMBIM6 12 50144403 promoter blood 26.69 0.00 439 ENST00000553070.5 NFE2 12 54694799 promoter blood 23.61 0.00 440 ENST00000558012.5 PSTPIP1 15 77287426 promoter blood 26.47 0.31 441 ENST00000559750.5 PSTPIP1 15 77287513 promoter blood 16.39 0.12 442 ENST00000564662.1 COTL1 16 84651681 promoter blood 10.13 0.81 443 ENST00000564905.1 XPO6 16 28145246 promoter blood 12.98 0.47 444 ENST00000568763.1 CORO1A 16 30194926 promoter blood 45.17 0.63 445 ENST00000570106.6 SIGLEC5 19 52133588 promoter blood 40.53 0.18 446 ENST00000572782.1 ARRB2 17 4617846 promoter blood 16.63 0.33 447 ENST00000576628.1 ACAP1 17 7239916 promoter blood 20.20 0.18 448 ENST00000577894.1 EVI2B 17 29641123 promoter blood 14.34 0.00 449 ENST00000578067.5 LIMD2 17 61777468 promoter blood 10.86 0.22 450 ENST00000578402.5 LIMD2 17 61778045 promoter blood 31.49 0.77 451 ENST00000585901.6 TYROBP 19 36399149 promoter blood 13.40 0.19 452 ENST00000586946.1 TYROBP 19 36399197 promoter blood 23.56 0.61 453 ENST00000587259.5 VMP1 17 57807076 promoter blood 10.58 0.05 454 ENST00000587856.1 FMNL1 17 43311251 promoter blood 22.20 0.28 455 ENST00000588673.3 OAZ1 19 2270290 promoter blood 24.28 0.69 456 ENST00000589614.5 TREM1 6 41254403 promoter blood 31.20 0.54 457 ENST00000589900.5 ICAM3 19 10450305 promoter blood 21.24 0.00 458 ENST00000592860.2 CFD 19 859664 promoter blood 16.53 0.85 459 ENST00000595042.5 FPR1 19 52255146 promoter blood 63.93 0.18 460 ENST00000595217.1 NKG7 19 51875955 promoter blood 33.26 0.52 461 ENST00000595325.5 MYO1F 19 8642322 promoter blood 13.66 0.09 462 ENST00000595636.1 GMFG 19 39826664 promoter blood 10.44 0.68 463 ENST00000595725.5 CD37 19 49838657 promoter blood 20.04 0.12 464 ENST00000595840.1 LRRC25 19 18508421 promoter blood 36.84 0.88 465 ENST00000596426.5 CD37 19 49838691 promoter blood 55.55 0.57 466 ENST00000596764.5 VAV1 19 6772739 promoter blood 12.25 0.59 467 ENST00000597852.5 CD37 19 49838675 promoter blood 13.98 0.20 468 ENST00000598034.5 GMFG 19 39826646 promoter blood 43.77 0.45 469 ENST00000599180.2 FFAR2 19 35939203 promoter blood 24.79 0.00 470 ENST00000599716.5 SHKBP1 19 41082793 promoter blood 10.66 0.22 471 ENST00000600626.1 C5AR2 19 47840371 promoter blood 12.99 0.11 472 ENST00000600972.1 JUND 19 18391739 promoter blood 17.49 0.60 473 ENST00000602185.5 GMFG 19 39826645 promoter blood 14.09 0.00 474 ENST00000602569.1 IFITM2 11 308217 promoter blood 3175.79 0.00 475 ENST00000605039.5 BIN2 12 51717938 promoter blood 11.02 0.11 476 ENST00000611028.2 FOLR3 11 71846798 promoter blood 11.13 0.00 477 ENST00000612844.4 FOLR3 11 71846756 promoter blood 13.11 0.00 478 ENST00000615439.4 RASGRP4 19 38916945 promoter blood 10.11 0.00 479 ENST00000615825.1 MME 3 154801957 promoter blood 12.37 0.88 480 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 0.07 481 ENST00000618265.4 CD177 19 43857811 promoter blood 222.54 0.73 482 ENST00000620541.4 RIN3 14 92980137 promoter blood 17.39 0.84 483 ENST00000620888.4 HBG2 11 5276011 promoter blood 161.14 0.00 484 ENST00000003084.10 CFTR 7 117120201 junction tumor 0.00 30.20 485 ENST00000027335.7 CDH17 8 95220711 junction tumor 0.00 149.83 486 ENST00000161006.7 PRSS22 16 2908024 junction tumor 0.00 10.29 487 ENST00000162330.9 BCAR1 16 75285369 junction tumor 0.00 16.86 488 ENST00000201586.6 SULT2B1 19 49055580 junction tumor 0.03 16.67 489 ENST00000211314.4 TMEM14A 6 52536043 junction tumor 0.67 25.17 490 ENST00000215582.7 MISP 19 751171 junction tumor 0.00 116.54 491 ENST00000215743.7 MMP11 22 24115165 junction tumor 0.08 42.41 492 ENST00000216968.4 PROCR 20 33760027 junction tumor 0.36 28.48 493 ENST00000221992.10 CEACAM5 19 42212714 junction tumor 0.00 1235.90 494 ENST00000223271.7 RARRES2 7 150038667 junction tumor 0.41 46.30 495 ENST00000226230.7 TMEM97 17 26646391 junction tumor 0.39 20.84 496 ENST00000226760.5 WFS1 4 6271741 junction tumor 0.35 15.01 497 ENST00000227868.8 PDHX 11 34938362 junction tumor 0.99 13.52 498 ENST00000228916.6 SCNN1A 12 6484671 junction tumor 0.05 32.36 499 ENST00000230588.8 MEP1A 6 46761204 junction tumor 0.00 21.95 500 ENST00000232458.9 ECT2 3 172468647 junction tumor 0.28 12.07 501 ENST00000245451.8 BMP4 14 54423268 junction tumor 0.00 16.43 502 ENST00000245907.10 C3 19 6720527 junction tumor 0.37 15.08 503 ENST00000250405.9 BCL2L2 14 23776103 junction tumor 1.00 11.63 504 ENST00000254260.7 RHPN2 19 33555690 junction tumor 0.03 23.49 505 ENST00000255681.6 MACROD1 11 63933169 junction tumor 0.54 22.18 506 ENST00000256585.9 REG4 1 120354032 junction tumor 0.09 37.82 507 ENST00000256951.9 EMP1 12 13349806 junction tumor 0.39 14.17 508 ENST00000260227.4 MMP7 11 102401324 junction tumor 0.00 29.38 509 ENST00000261769.9 CDH1 16 68771366 junction tumor 0.00 123.30 510 ENST00000262429.8 ATP2C2 16 84402320 junction tumor 0.34 16.47 511 ENST00000262753.8 POF1B X 84634644 junction tumor 0.02 40.41 512 ENST00000263629.8 MTIF2 2 55496305 junction tumor 0.85 13.76 513 ENST00000263735.8 EPCAM 2 47596720 junction tumor 0.11 594.54 514 ENST00000263895.8 RND3 2 151344063 junction tumor 0.00 10.29 515 ENST00000264144.4 LAMC2 1 183155566 junction tumor 0.01 31.46 516 ENST00000264748.6 FGFRL1 4 1006352 junction tumor 0.82 17.03 517 ENST00000266980.8 SLC39A5 12 56624657 junction tumor 0.00 20.87 518 ENST00000267101.7 ERBB3 12 56474166 junction tumor 0.00 40.98 519 ENST00000267814.13 SORD 15 45315547 junction tumor 0.93 13.70 520 ENST00000267996.11 TPM1 15 63335142 junction tumor 0.87 32.98 521 ENST00000269571.9 ERBB2 17 37856564 junction tumor 0.00 11.47 522 ENST00000270560.3 TM4SF5 17 4675394 junction tumor 0.00 18.39 523 ENST00000271064.11 TINAGL1 1 32042196 junction tumor 0.10 42.75 524 ENST00000278559.7 CAPN5 11 76778141 junction tumor 0.52 27.31 525 ENST00000278937.6 MPZL2 11 118134811 junction tumor 0.37 17.05 526 ENST00000288937.6 MRPL17 11 6704354 junction tumor 0.85 16.44 527 ENST00000290130.3 MIS18A 21 33650992 junction tumor 0.49 12.76 528 ENST00000290913.7 CHCHD6 3 126423242 junction tumor 0.65 15.07 529 ENST00000291525.11 TFF3 21 43735403 junction tumor 0.00 209.02 530 ENST00000292401.8 AZGP1 7 99573568 junction tumor 0.14 45.24 531 ENST00000292408.8 FGFR4 5 176514078 junction tumor 0.07 25.86 532 ENST00000295092.2 FAM84A 2 14773061 junction tumor 0.00 13.18 533 ENST00000296129.5 CDCP1 3 45187698 junction tumor 0.11 15.27 534 ENST00000296252.8 LIPH 3 185270211 junction tumor 0.03 12.23 535 ENST00000296424.8 BDH2 4 104020940 junction tumor 0.99 14.16 536 ENST00000296666.12 PRRC1 5 126853468 junction tumor 0.95 11.62 537 ENST00000297205.6 STEAP1 7 89783857 junction tumor 0.00 14.91 538 ENST00000299610.4 MFAP4 17 19290463 junction tumor 0.39 15.19 539 ENST00000299714.7 SEC11C 18 56807267 junction tumor 0.62 11.38 540 ENST00000300119.7 MYO1A 12 57443671 junction tumor 0.00 15.11 541 ENST00000300283.10 CKMT1B 15 43885469 junction tumor 0.00 35.88 542 ENST00000300557.2 PRR15L 17 46035023 junction tumor 0.03 96.21 543 ENST00000301395.7 GGT6 17 4463677 junction tumor 0.00 16.81 544 ENST00000301887.8 BATF2 11 64764348 junction tumor 0.43 11.12 545 ENST00000307078.9 AXIN2 17 63557568 junction tumor 0.09 14.10 546 ENST00000308302.3 GOLT1A 1 204183010 junction tumor 0.03 12.22 547 ENST00000308831.6 RHOD 11 66824505 junction tumor 0.07 10.41 548 ENST00000310398.6 AGR3 7 16921568 junction tumor 0.00 33.08 549 ENST00000310706.9 JUP 17 39942840 junction tumor 0.87 86.21 550 ENST00000310836.10 UGT8 4 115520130 junction tumor 0.04 14.08 551 ENST00000311160.13 TNS3 7 47621649 junction tumor 0.68 16.18 552 ENST00000311381.7 C6orf203 6 107349475 junction tumor 0.93 14.55 553 ENST00000311620.6 ANKS4B 16 21245222 junction tumor 0.00 10.61 554 ENST00000316673.8 HNF4A 20 42984493 junction tumor 0.00 10.78 555 ENST00000317508.10 PRSS8 16 31146735 junction tumor 0.11 143.22 556 ENST00000318024.8 USH1C 11 17565819 junction tumor 0.00 46.62 557 ENST00000318407.4 BOK 2 242498408 junction tumor 0.57 13.75 558 ENST00000318443.9 CD276 15 73976801 junction tumor 0.00 11.45 559 ENST00000318683.6 B3GNT3 19 17906015 junction tumor 0.00 57.75 560 ENST00000319838.9 GPR35 2 241544987 junction tumor 0.31 30.59 561 ENST00000322536.7 DDX10 11 108536066 junction tumor 0.75 10.84 562 ENST00000324038.6 FAM101A 12 124773916 junction tumor 0.00 10.08 563 ENST00000325307.11 HMGB3 X 150151849 junction tumor 0.30 14.09 564 ENST00000325568.9 IL32 16 3115495 junction tumor 0.93 14.52 565 ENST00000326587.11 MAGED1 X 51636851 junction tumor 0.60 16.14 566 ENST00000329875.12 PYCR1 17 79894624 junction tumor 0.12 36.33 567 ENST00000331595.8 BGN X 152760571 junction tumor 0.60 74.92 568 ENST00000332149.9 TMPRSS2 21 42880008 junction tumor 0.02 43.57 569 ENST00000333090.4 TSKU 11 76494448 junction tumor 0.00 17.21 570 ENST00000334047.11 F3 1 95007093 junction tumor 0.08 13.07 571 ENST00000334869.8 LGMN 14 93214834 junction tumor 0.94 45.73 572 ENST00000337682.8 FAM60A 12 31478958 junction tumor 0.97 25.73 573 ENST00000338660.5 VWA1 1 1371201 junction tumor 0.06 21.82 574 ENST00000339276.5 SFN 1 27190948 junction tumor 0.60 113.82 575 ENST00000340556.10 MORN2 2 39103251 junction tumor 0.33 11.41 576 ENST00000344616.3 S100A14 1 153588771 junction tumor 0.00 143.55 577 ENST00000350051.7 BIRC5 17 76210508 junction tumor 0.63 18.32 578 ENST00000352551.9 UBE2C 20 44441435 junction tumor 0.00 10.99 579 ENST00000354624.5 HKDC1 10 70980254 junction tumor 0.14 20.07 580 ENST00000354900.7 LSR 19 35740034 junction tumor 0.75 31.22 581 ENST00000355097.6 ENTPD2 9 139948333 junction tumor 0.03 10.14 582 ENST00000355808.9 PDHA1 X 19362212 junction tumor 0.25 16.21 583 ENST00000355899.7 PLS3 X 114795587 junction tumor 0.00 12.05 584 ENST00000356509.7 GMNN 6 24775340 junction tumor 0.57 11.97 585 ENST00000356762.7 CRB3 19 6464361 junction tumor 0.00 12.29 586 ENST00000357166.10 ZDHHC9 X 128977672 junction tumor 0.29 20.11 587 ENST00000357602.7 IPO5 13 98612657 junction tumor 0.80 15.40 588 ENST00000358432.7 EPHA2 1 16482343 junction tumor 0.03 23.85 589 ENST00000358813.4 CCL20 2 228678703 junction tumor 0.00 33.26 590 ENST00000358867.10 TMEM126B 11 85339732 junction tumor 0.47 17.68 591 ENST00000360325.11 CLDN7 17 7165140 junction tumor 0.09 133.65 592 ENST00000360605.8 URI1 19 30414661 junction tumor 0.44 12.86 593 ENST00000360760.9 SPATS2L 2 201171324 junction tumor 0.73 32.04 594 ENST00000360779.3 SDCBP2 20 1309729 junction tumor 0.00 17.84 595 ENST00000361084.9 RAB25 1 156031234 junction tumor 0.07 131.50 596 ENST00000361852.8 EPS8L3 1 110306444 junction tumor 0.00 26.64 597 ENST00000361901.6 CALD1 7 134464500 junction tumor 0.42 33.93 598 ENST00000366787.7 THBS2 6 169654085 junction tumor 0.07 14.23 599 ENST00000366999.8 NEK2 1 211848726 junction tumor 0.16 11.93 600 ENST00000367274.8 UBE2T 1 202311023 junction tumor 0.63 29.13 601 ENST00000367283.7 ELF3 1 201979948 junction tumor 0.07 135.46 602 ENST00000367284.9 ELF3 1 201979834 junction tumor 0.02 50.55 603 ENST00000367313.4 LAD1 1 201368538 junction tumor 0.05 100.09 604 ENST00000367976.3 CTGF 6 132272247 junction tumor 0.32 44.18 605 ENST00000368408.3 EFNA3 1 155051545 junction tumor 0.36 18.08 606 ENST00000368554.8 PRAP1 10 135122967 junction tumor 0.00 32.41 607 ENST00000369406.7 HMGCS2 1 120311364 junction tumor 0.00 17.63 608 ENST00000370481.8 GBP3 1 89488367 junction tumor 0.66 12.56 609 ENST00000370828.3 GPC4 X 132548834 junction tumor 0.03 13.27 610 ENST00000371221.3 ALDH18A1 10 97416354 junction tumor 0.04 29.55 611 ENST00000372486.5 NTMT1 9 132371457 junction tumor 0.00 14.12 612 ENST00000372966.7 NOX1 X 100129084 junction tumor 0.00 48.52 613 ENST00000373255.8 H2AFY2 10 71812756 junction tumor 0.42 12.60 614 ENST00000373290.6 TSPAN15 10 71211446 junction tumor 0.30 60.96 615 ENST00000373669.6 PIN4 X 71401678 junction tumor 0.87 13.81 616 ENST00000373699.5 PPIL1 6 36842493 junction tumor 0.85 17.26 617 ENST00000373944.7 ZWINT 10 58120957 junction tumor 0.38 16.27 618 ENST00000374183.4 BSPRY 9 116112060 junction tumor 0.22 15.59 619 ENST00000374214.3 UQCC2 6 33679326 junction tumor 1.00 17.77 620 ENST00000374837.7 MAP1LC3A 20 33134720 junction tumor 0.87 16.45 621 ENST00000375431.8 GRTP1 13 114018335 junction tumor 0.05 18.16 622 ENST00000376569.7 DDR1 6 30851922 junction tumor 0.08 11.00 623 ENST00000376652.8 ENTPD6 20 25176503 junction tumor 0.44 14.06 624 ENST00000378115.2 ARHGEF35 7 143892631 junction tumor 0.10 13.16 625 ENST00000378378.8 ARHGEF16 1 3371375 junction tumor 0.00 12.12 626 ENST00000378427.5 FAM213B 1 2518387 junction tumor 0.59 12.06 627 ENST00000379046.6 NQO1 16 69760336 junction tumor 0.07 39.35 628 ENST00000379715.9 EEF1E1 6 8102668 junction tumor 0.59 17.82 629 ENST00000379742.4 POSTN 13 38172745 junction tumor 0.01 11.69 630 ENST00000379923.5 ACO1 9 32384733 junction tumor 0.81 16.28 631 ENST00000380071.7 RFC3 13 34392402 junction tumor 0.48 15.11 632 ENST00000381134.7 ARSE X 2882265 junction tumor 0.00 24.51 633 ENST00000382848.4 GJB2 13 20766922 junction tumor 0.09 18.88 634 ENST00000389614.5 GPX2 14 65409223 junction tumor 0.10 652.10 635 ENST00000391967.6 LAD1 1 201368397 junction tumor 0.00 16.64 636 ENST00000393316.7 BCL2L15 1 114429871 junction tumor 0.11 11.11 637 ENST00000393366.6 ATP5G1 17 46970272 junction tumor 0.63 40.08 638 ENST00000393725.6 KIAA1191 5 175788605 junction tumor 0.75 11.70 639 ENST00000394201.8 SCOC 4 141294871 junction tumor 0.53 14.61 640 ENST00000394265.5 PPP1R1B 17 37784875 junction tumor 0.00 81.30 641 ENST00000394267.2 PPP1R1B 17 37784959 junction tumor 0.00 87.42 642 ENST00000395641.2 NUPR1 16 28550117 junction tumor 0.45 37.05 643 ENST00000397542.6 CDHR5 11 624818 junction tumor 0.02 18.38 644 ENST00000397714.6 SEPTIN10 2 110371375 junction tumor 0.14 14.96 645 ENST00000397995.2 RNASE4 14 21152855 junction tumor 0.56 10.20 646 ENST00000401412.5 AGR2 7 16844577 junction tumor 0.00 103.38 647 ENST00000403444.7 CEACAM1 19 43032463 junction tumor 0.00 33.67 648 ENST00000405271.5 EPCAM 2 47572362 junction tumor 0.00 20.99 649 ENST00000410036.2 MZT2A 2 132250293 junction tumor 0.00 12.64 650 ENST00000416348.1 ADIRF 10 88728362 junction tumor 0.00 22.43 651 ENST00000419304.6 AGR2 7 16844559 junction tumor 0.00 257.72 652 ENST00000419308.6 FOXA2 20 22564830 junction tumor 0.00 13.51 653 ENST00000420892.1 HTRA1 10 124266401 junction tumor 0.98 24.46 654 ENST00000423485.5 TOP2A 17 38574023 junction tumor 0.44 31.06 655 ENST00000425042.6 HID1 17 72968686 junction tumor 0.23 13.99 656 ENST00000425340.2 FUT2 19 49199346 junction tumor 0.02 13.10 657 ENST00000428445.1 VARS 6 31750307 junction tumor 0.78 10.22 658 ENST00000428849.6 KIFC1 6 33359774 junction tumor 0.60 17.24 659 ENST00000429772.6 TMEM106C 12 48357487 junction tumor 0.70 34.02 660 ENST00000430118.1 HMGB3 X 150154222 junction tumor 0.52 12.82 661 ENST00000433307.2 PLEKHA1 10 124152857 junction tumor 0.98 13.38 662 ENST00000441275.5 BDH1 3 197282652 junction tumor 0.87 17.80 663 ENST00000444124.6 DDC 7 50632982 junction tumor 0.00 21.66 664 ENST00000448599.2 PHGR1 15 40643263 junction tumor 0.00 289.14 665 ENST00000450427.1 PRR15 7 29605369 junction tumor 0.00 10.59 666 ENST00000450894.7 ITGB4 17 73717692 junction tumor 0.14 50.86 667 ENST00000452441.5 DDR1 6 30852487 junction tumor 0.07 51.62 668 ENST00000455712.5 POLR2H 3 184080512 junction tumor 0.94 11.92 669 ENST00000463201.2 PRAP1 10 135164937 junction tumor 0.00 54.46 670 ENST00000467415.5 TMEM14C 6 10723474 junction tumor 0.69 26.73 671 ENST00000467905.5 AK2 1 33502337 junction tumor 0.00 11.87 672 ENST00000469862.1 CENPF 1 214828746 junction tumor 0.39 10.26 673 ENST00000472782.1 ATP5G3 2 176046384 junction tumor 0.62 10.87 674 ENST00000476587.1 NDUFB5 3 179334832 junction tumor 0.89 14.92 675 ENST00000478194.1 FERMT1 20 6074721 junction tumor 0.00 27.00 676 ENST00000478869.1 WDR12 2 203765748 junction tumor 0.71 14.50 677 ENST00000479419.1 IFT172 2 27668796 junction tumor 0.00 37.10 678 ENST00000484713.1 LAMB2 3 49158866 junction tumor 0.41 13.87 679 ENST00000489477.1 NDUFAF4 6 97345542 junction tumor 0.66 10.30 680 ENST00000490807.5 NTPCR 1 233086490 junction tumor 0.77 10.54 681 ENST00000494446.1 FN1 2 216230228 junction tumor 0.79 52.10 682 ENST00000494801.5 TCEAL4 X 102840552 junction tumor 0.60 13.59 683 ENST00000495558.1 VWA1 1 1370526 junction tumor 0.00 13.92 684 ENST00000496195.1 GLRX3 10 131977684 junction tumor 0.98 10.30 685 ENST00000497734.5 SRC 20 35973290 junction tumor 0.00 12.44 686 ENST00000507614.1 TIMM8B 11 111957364 junction tumor 0.80 10.54 687 ENST00000507699.1 PALLD 4 169819865 junction tumor 0.31 14.56 688 ENST00000514985.5 SEPP1 5 42811938 junction tumor 0.59 49.95 689 ENST00000520271.5 COX6C 8 100905671 junction tumor 0.51 12.86 690 ENST00000523677.5 C1orf210 1 43751115 junction tumor 0.00 13.49 691 ENST00000524832.5 CHID1 11 902198 junction tumor 0.42 10.82 692 ENST00000525657.1 C1QTNF5 11 119211405 junction tumor 0.05 17.27 693 ENST00000526202.5 LMO7 13 76334967 junction tumor 0.09 23.11 694 ENST00000527106.5 FUT6 19 5838688 junction tumor 0.00 13.22 695 ENST00000528430.2 PPP1R16A 8 145726677 junction tumor 0.92 22.33 696 ENST00000530094.5 CTNND1 11 57529518 junction tumor 0.00 26.61 697 ENST00000533827.5 VPS51 11 64877063 junction tumor 0.00 12.01 698 ENST00000534378.5 ILVBL 19 15236467 junction tumor 0.64 11.41 699 ENST00000537496.5 MMAB 12 110011152 junction tumor 0.93 12.43 700 ENST00000541754.1 NNMT 11 114168120 junction tumor 0.72 23.55 701 ENST00000542056.1 GPRC5A 12 13044598 junction tumor 0.00 23.91 702 ENST00000543445.5 LDHA 11 18416188 junction tumor 0.00 71.47 703 ENST00000543623.5 PLCD3 17 43192462 junction tumor 0.27 14.58 704 ENST00000546314.5 STARD10 11 72493311 junction tumor 0.00 31.66 705 ENST00000546485.5 RPL41 12 56510443 junction tumor 0.75 48.15 706 ENST00000547281.5 CDK4 12 58145958 junction tumor 0.83 30.31 707 ENST00000547838.2 FAM109A 12 111801492 junction tumor 0.94 11.49 708 ENST00000548169.2 ATP2A2 12 110729929 junction tumor 0.34 13.63 709 ENST00000552128.2 TSPAN8 12 71532931 junction tumor 0.00 15.81 710 ENST00000552561.5 TMEM106C 12 48357416 junction tumor 0.38 17.25 711 ENST00000554989.1 CKB 14 103987600 junction tumor 0.75 83.82 712 ENST00000557049.1 GPX2 14 65409385 junction tumor 0.00 18.28 713 ENST00000558580.1 SORD 15 45328542 junction tumor 0.95 15.73 714 ENST00000559087.5 BMP4 14 54423477 junction tumor 0.00 13.08 715 ENST00000562684.5 HN1L 16 1728357 junction tumor 0.25 19.21 716 ENST00000564043.1 NQO1 16 69760404 junction tumor 0.32 89.24 717 ENST00000581920.1 TYMS 18 667752 junction tumor 0.88 11.79 718 ENST00000583327.2 ITGB4 17 73747929 junction tumor 0.12 32.84 719 ENST00000586005.5 SMIM22 16 4845450 junction tumor 0.00 103.03 720 ENST00000587251.5 LGALS3BP 17 76975906 junction tumor 0.00 48.36 721 ENST00000588605.5 C19orf33 19 38794923 junction tumor 0.22 18.46 722 ENST00000589378.5 TJP3 19 3721908 junction tumor 0.13 11.74 723 ENST00000591795.1 DENND1C 19 6469607 junction tumor 0.56 11.26 724 ENST00000594443.5 FBL 19 40336931 junction tumor 0.00 19.57 725 ENST00000594605.5 STAP2 19 4338649 junction tumor 0.06 27.33 726 ENST00000595110.1 FAM83E 19 49117965 junction tumor 0.00 13.13 727 ENST00000597153.5 LGALS4 19 39303482 junction tumor 0.00 20.51 728 ENST00000601623.5 LSR 19 35740271 junction tumor 0.21 24.39 729 ENST00000610552.4 SLC2A8 9 130159565 junction tumor 0.65 11.38 730 ENST00000612794.1 GPX2 14 65409328 junction tumor 0.00 23.73 731 ENST00000612809.4 C8orf59 8 86132535 junction tumor 0.94 54.53 732 ENST00000616154.1 CDX1 5 149546475 junction tumor 0.00 138.07 733 ENST00000616727.4 MUC13 3 124653505 junction tumor 0.01 221.05 734 ENST00000618855.4 TMPRSS4 11 117948020 junction tumor 0.00 10.45 735 ENST00000619895.4 TMC4 19 54676734 junction tumor 0.35 33.05 736 ENST00000620753.4 EI24 11 125439410 junction tumor 0.63 12.17 737 ENST00000008938.4 PGLYRP1 19 46525993 junction blood 148.76 0.05 738 ENST00000199708.2 HBQ1 16 230580 junction blood 45.79 0.00 739 ENST00000216338.8 GZMH 14 25078765 junction blood 15.58 0.99 740 ENST00000221515.5 RETN 19 7734007 junction blood 72.49 0.19 741 ENST00000221954.6 CEACAM4 19 42133268 junction blood 32.81 0.13 742 ENST00000225538.3 P2RX1 17 3819383 junction blood 15.55 0.30 743 ENST00000232014.8 BCL6 3 187453878 junction blood 19.07 0.18 744 ENST00000234347.9 PRTN3 19 841069 junction blood 13.78 0.00 745 ENST00000236826.7 MMP8 11 102595485 junction blood 20.68 0.04 746 ENST00000244709.8 TREM1 6 41254345 junction blood 67.12 0.63 747 ENST00000246115.4 S1PR4 19 3180330 junction blood 127.44 0.94 748 ENST00000246549.2 FFAR2 19 35942667 junction blood 58.85 0.34 749 ENST00000246657.2 CCR7 17 38721652 junction blood 11.89 0.75 750 ENST00000259396.8 ORM1 9 117085527 junction blood 34.89 0.14 751 ENST00000262407.5 ITGA2B 17 42466654 junction blood 12.34 0.04 752 ENST00000264972.9 ZAP70 2 98330137 junction blood 15.69 0.72 753 ENST00000279452.10 CD44 11 35198287 junction blood 10.76 0.00 754 ENST00000281703.10 GLT1D1 12 129338194 junction blood 22.75 0.02 755 ENST00000290075.10 SLC25A37 8 23386725 junction blood 45.08 0.87 756 ENST00000292432.9 HK3 5 176326268 junction blood 98.07 0.60 757 ENST00000295683.2 CXCR1 2 219031631 junction blood 355.57 0.18 758 ENST00000296435.2 CAMP 3 48265202 junction blood 27.17 0.06 759 ENST00000296487.8 PPM1M 3 52280330 junction blood 13.09 0.41 760 ENST00000297239.10 SYTL3 6 159082417 junction blood 10.79 0.54 761 ENST00000299663.7 CLEC4E 12 8693357 junction blood 29.27 0.20 762 ENST00000302017.3 ZNF467 7 149470197 junction blood 25.10 0.54 763 ENST00000303531.11 PRKCB 16 23847669 junction blood 16.08 0.36 764 ENST00000303757.12 LST1 6 31555095 junction blood 11.09 0.23 765 ENST00000307564.8 AKNA 9 117156637 junction blood 11.95 0.38 766 ENST00000310544.8 PHOSPHO1 17 47307830 junction blood 30.92 0.08 767 ENST00000318507.6 CXCR2 2 218991076 junction blood 157.27 0.28 768 ENST00000326165.10 CD300LF 17 72708963 junction blood 18.99 0.70 769 ENST00000328118.7 FMNL1 17 43299554 junction blood 11.80 0.41 770 ENST00000329021.9 NFAM1 22 42828243 junction blood 43.63 0.94 771 ENST00000329410.3 C16orf54 16 29757232 junction blood 24.31 0.49 772 ENST00000332549.7 IL1R2 2 102608473 junction blood 112.29 0.55 773 ENST00000336577.8 MMP25 16 3097017 junction blood 194.37 0.54 774 ENST00000336906.4 HBG2 11 5275867 junction blood 104.85 0.00 775 ENST00000338372.6 VSTM1 19 54566998 junction blood 10.71 0.00 776 ENST00000342571.7 MKNK1 1 47051546 junction blood 14.42 0.02 777 ENST00000343534.9 C1orf162 1 112016652 junction blood 37.68 0.74 778 ENST00000346667.8 IKZF1 7 50344518 junction blood 11.73 0.24 779 ENST00000352818.8 CD44 11 35160917 junction blood 14.11 0.00 780 ENST00000354352.9 SLC11A1 2 219247098 junction blood 111.80 0.63 781 ENST00000355524.7 FCAR 19 55385779 junction blood 53.04 0.07 782 ENST00000356815.3 HBM 16 216088 junction blood 163.82 0.00 783 ENST00000356838.7 TMEM71 8 133772722 junction blood 16.78 0.36 784 ENST00000356864.3 TNFRSF10C 8 22960694 junction blood 108.86 0.56 785 ENST00000357198.8 DOK3 5 176936803 junction blood 66.68 0.74 786 ENST00000357260.5 FAM212B 1 112281808 junction blood 12.23 0.67 787 ENST00000358375.8 OSCAR 19 54604047 junction blood 18.93 0.28 788 ENST00000367025.7 TRAF3IP3 1 209929654 junction blood 17.52 0.64 789 ENST00000367053.5 CR1 1 207669733 junction blood 10.47 0.02 790 ENST00000367535.7 NCF2 1 183559291 junction blood 75.23 0.98 791 ENST00000367568.4 STX11 6 144471840 junction blood 24.42 0.79 792 ENST00000367972.8 FCGR2A 1 161475342 junction blood 27.69 0.40 793 ENST00000368015.1 ARHGAP30 1 161039410 junction blood 20.61 0.58 794 ENST00000368732.5 S100A8 1 153363333 junction blood 53.91 0.00 795 ENST00000368737.4 S100A12 1 153348028 junction blood 1099.02 0.31 796 ENST00000371806.3 FCN1 9 137809615 junction blood 379.64 0.88 797 ENST00000373103.5 CSF3R 1 36948412 junction blood 61.20 0.04 798 ENST00000373925.5 THEMIS2 1 28199176 junction blood 12.15 0.53 799 ENST00000374005.7 FGR 1 27961576 junction blood 32.42 0.29 800 ENST00000374163.5 RPS6KA1 1 26872526 junction blood 17.41 0.87 801 ENST00000375448.4 PADI4 1 17634809 junction blood 95.04 0.03 802 ENST00000375862.6 HCK 20 30640289 junction blood 20.11 0.09 803 ENST00000376670.7 GATA1 X 48645053 junction blood 11.17 0.01 804 ENST00000377497.7 RASGRP2 11 64512214 junction blood 48.02 0.55 805 ENST00000378023.8 FAM65B 6 24877179 junction blood 15.67 0.00 806 ENST00000379400.7 RASSF2 20 4804203 junction blood 13.75 0.82 807 ENST00000380299.3 HBD 11 5255572 junction blood 138.84 0.07 808 ENST00000381112.7 CCM2 7 45067396 junction blood 17.78 0.00 809 ENST00000381153.7 C11orf21 11 2322986 junction blood 11.33 0.09 810 ENST00000381603.7 SIRPB1 20 1600515 junction blood 26.01 0.00 811 ENST00000391750.5 LILRB3 19 54727293 junction blood 65.61 0.41 812 ENST00000393450.5 MYL4 17 45286923 junction blood 22.77 0.00 813 ENST00000393847.5 DPEP2 16 68033278 junction blood 24.04 0.44 814 ENST00000394991.7 SNCA 4 90758113 junction blood 32.19 0.35 815 ENST00000397147.6 NCF4 22 37257245 junction blood 154.32 0.92 816 ENST00000398421.6 NCF1 7 74188450 junction blood 11.04 0.04 817 ENST00000399173.5 FGR 1 27952557 junction blood 101.05 0.26 818 ENST00000399753.2 MSRB1 16 1993103 junction blood 11.22 0.15 819 ENST00000409220.5 ARHGAP25 2 69002552 junction blood 23.89 0.31 820 ENST00000409930.3 IL1RN 2 113885317 junction blood 21.18 0.85 821 ENST00000416215.6 PTPN6 12 7060683 junction blood 12.72 0.88 822 ENST00000422400.6 VNN2 6 133078810 junction blood 14.59 0.10 823 ENST00000423345.4 PRAM1 19 8567449 junction blood 25.32 0.30 824 ENST00000433194.6 CDK5RAP2 9 123165594 junction blood 22.55 0.52 825 ENST00000441002.1 IL1R2 2 102625104 junction blood 16.30 0.00 826 ENST00000445347.1 LILRB3 19 54726815 junction blood 49.26 0.10 827 ENST00000445961.5 RPS9 19 54704829 junction blood 14.72 0.89 828 ENST00000447110.5 PIK3R5 17 8868913 junction blood 12.89 0.29 829 ENST00000449131.6 BEST1 11 61717899 junction blood 13.35 0.54 830 ENST00000454703.6 ACSL1 4 185747070 junction blood 35.07 0.78 831 ENST00000460442.5 ZDHHC19 3 195925660 junction blood 22.43 0.04 832 ENST00000464431.1 ABTB1 3 127395274 junction blood 20.22 0.70 833 ENST00000464465.6 CSF3R 1 36937034 junction blood 259.11 0.50 834 ENST00000465814.5 ARAP1 11 72432895 junction blood 10.09 0.58 835 ENST00000467786.1 FGD3 9 95737687 junction blood 43.15 0.29 836 ENST00000474085.5 IL1R2 2 102638711 junction blood 24.35 0.04 837 ENST00000475226.1 HBB 11 5247807 junction blood 2709.48 0.00 838 ENST00000477801.1 S100A8 1 153362871 junction blood 161.47 0.07 839 ENST00000480395.5 TRIM22 11 5717885 junction blood 17.36 0.70 840 ENST00000481568.2 C10orf54 10 73521355 junction blood 31.27 0.90 841 ENST00000483750.5 WAS X 48542374 junction blood 34.49 0.17 842 ENST00000485743.1 HBB 11 5248160 junction blood 128.52 0.00 843 ENST00000485928.5 PHC2 1 33815198 junction blood 11.05 0.73 844 ENST00000486097.1 NCF1 7 74197975 junction blood 12.51 0.06 845 ENST00000487540.6 CSF3R 1 36937839 junction blood 47.30 0.17 846 ENST00000488171.5 CD55 1 207495210 junction blood 25.43 0.43 847 ENST00000488945.5 GNLY 2 85912344 junction blood 11.68 0.09 848 ENST00000489358.5 NAMPT 7 105925274 junction blood 30.07 0.00 849 ENST00000491955.5 MPP1 X 154009875 junction blood 10.84 0.42 850 ENST00000493242.1 LILRB2 19 54784816 junction blood 22.65 0.13 851 ENST00000494185.1 LMNB1 5 126147590 junction blood 10.53 0.00 852 ENST00000496823.1 BCL6 3 187463198 junction blood 21.33 0.20 853 ENST00000497259.5 ARHGAP25 2 69034612 junction blood 25.49 0.72 854 ENST00000497920.1 ARID5A 2 97213254 junction blood 11.90 0.30 855 ENST00000509314.5 FBXL5 4 15661350 junction blood 10.24 0.00 856 ENST00000509339.1 MXD3 5 176734782 junction blood 30.07 0.08 857 ENST00000510784.6 FAM65B 6 25042079 junction blood 61.47 0.19 858 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 0.10 859 ENST00000520174.5 DMTN 8 21914647 junction blood 16.02 0.00 860 ENST00000523022.5 CA1 8 86290275 junction blood 40.92 0.11 861 ENST00000525270.5 VNN2 6 133084522 junction blood 38.37 0.12 862 ENST00000527146.1 IFITM2 11 308438 junction blood 18.56 0.63 863 ENST00000528780.5 IFITM1 11 313691 junction blood 47.88 0.31 864 ENST00000529635.5 TBC1D10C 11 67171825 junction blood 16.89 0.34 865 ENST00000533968.1 SPI1 11 47399860 junction blood 12.90 0.22 866 ENST00000535669.6 CD37 19 49838866 junction blood 33.70 0.19 867 ENST00000540998.5 CDC42SE1 1 151031955 junction blood 10.52 0.00 868 ENST00000542481.1 ATG16L2 11 72535167 junction blood 25.18 0.37 869 ENST00000543576.5 DENND1C 19 6481690 junction blood 12.06 0.00 870 ENST00000544232.5 TMEM91 19 41882759 junction blood 12.57 0.20 871 ENST00000544665.7 ITGAM 16 31271413 junction blood 56.38 0.99 872 ENST00000546704.1 ARHGAP9 12 57868658 junction blood 19.20 0.13 873 ENST00000552370.5 TMBIM6 12 50144488 junction blood 26.69 0.00 874 ENST00000553070.5 NFE2 12 54694585 junction blood 23.61 0.00 875 ENST00000558012.5 PSTPIP1 15 77287950 junction blood 26.47 0.31 876 ENST00000564662.1 COTL1 16 84651107 junction blood 10.13 0.81 877 ENST00000564905.1 XPO6 16 28145162 junction blood 12.98 0.47 878 ENST00000568763.1 CORO1A 16 30195046 junction blood 45.17 0.63 879 ENST00000570106.6 SIGLEC5 19 52133552 junction blood 40.53 0.18 880 ENST00000572782.1 ARRB2 17 4618338 junction blood 16.63 0.33 881 ENST00000576628.1 ACAP1 17 7240106 junction blood 20.20 0.18 882 ENST00000577894.1 EVI2B 17 29640997 junction blood 14.34 0.00 883 ENST00000578067.5 LIMD2 17 61776617 junction blood 10.86 0.22 884 ENST00000578402.5 LIMD2 17 61777729 junction blood 31.49 0.77 885 ENST00000585901.6 TYROBP 19 36399070 junction blood 13.40 0.19 886 ENST00000586946.1 TYROBP 19 36399077 junction blood 23.56 0.61 887 ENST00000587259.5 VMP1 17 57807378 junction blood 10.58 0.05 888 ENST00000587856.1 FMNL1 17 43311567 junction blood 22.20 0.28 889 ENST00000588673.3 OAZ1 19 2270675 junction blood 24.28 0.69 890 ENST00000589900.5 ICAM3 19 10450215 junction blood 21.24 0.00 891 ENST00000592860.2 CFD 19 859765 junction blood 16.53 0.85 892 ENST00000595042.5 FPR1 19 52255067 junction blood 63.93 0.18 893 ENST00000595217.1 NKG7 19 51875633 junction blood 33.26 0.52 894 ENST00000595325.5 MYO1F 19 8642191 junction blood 13.66 0.09 895 ENST00000595636.1 GMFG 19 39826614 junction blood 10.44 0.68 896 ENST00000595840.1 LRRC25 19 18508263 junction blood 36.84 0.88 897 ENST00000596764.5 VAV1 19 6773022 junction blood 12.25 0.59 898 ENST00000597852.5 CD37 19 49838832 junction blood 13.98 0.20 899 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 0.00 900 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 0.22 901 ENST00000600626.1 C5AR2 19 47840426 junction blood 12.99 0.11 902 ENST00000600972.1 JUND 19 18391266 junction blood 17.49 0.60 903 ENST00000605039.5 BIN2 12 51717806 junction blood 11.02 0.11 904 ENST00000611028.2 FOLR3 11 71846814 junction blood 11.13 0.00 905 ENST00000615439.4 RASGRP4 19 38916709 junction blood 10.11 0.00 906 ENST00000615825.1 MME 3 154802116 junction blood 12.37 0.88 907 ENST00000618265.4 CD177 19 43857918 junction blood 222.54 0.73 908 ENST00000620541.4 RIN3 14 92980320 junction blood 17.39 0.84 Columns ID: feature index Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood FPKM_(tumor): FPKM value in tumor of colorectal cancer

TABLE S4 Coefficients for the selected NDRs in the trained models (CRC model and CRC + BRCA model). CRC model Feature Gene Transcript Region Group Coefficient 1 SHKBP1 ENST00000599716 junction blood 0.607 2 ACSL1 ENST00000454703 junction blood 0.431 3 BCAR1 ENST00000162330 junction tumor −0.321 4 RAB25 ENST00000361084 promoter tumor −0.213 5 PRTN3 ENST00000234347 promoter blood 0.062 6 LSR ENST00000605618 promoter tumor −0.174 Columns Gene: gene name Transcript: transcript ID Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor Coefficient: value of the regression coefficient. The intercept value is 0.4368. CRC + BRCA model Feature Gene Transcript Region Group Coefficient 1 SLC11A1 ENST00000465984 promoter blood 0.150 2 NLRP12 ENST00000324134 promoter blood 0.181 3 PRTN3 ENST00000234347 promoter blood 0.124 4 HMBS ENST00000392841 promoter blood 0.251 5 LILRB3 ENST00000460208 promoter blood 0.140 6 ACSL1 ENST00000513001 junction blood 0.106 7 GP9 ENST00000307395 junction blood 0.251 8 MX2 ENST00000398632 promoter blood 0.106 9 RASGRP4 ENST00000615340 promoter blood 0.222 10 ATG16L2 ENST00000542481 promoter blood 0.166 Columns Gene: gene name Transcript: transcript ID Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor Coefficient: value of the regression coefficient. The intercept value is −1.3719.

TABLE S4 Columns Gene: gene name Transcript: transcript ID Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor Coefficient: value of the regression coefficient. The intercept value is 0.4368. Coefficients for the selected NDRs in the trained models (CRC model and CRC + BRCA model). CRC model Feature Gene T ranscript Region Group Coefficient 1 SHKBP1 ENST00000599716 junction blood 0.607 2 ACSL1 ENST00000454703 junction blood 0.431 3 BCAR1 ENST00000162330 junction tumor -0.321 4 RAB25 ENST00000361084 promoter tumor -0.213 5 PRTN3 ENST00000234347 promoter blood 0.062 6 LSR ENST00000605618 promoter tumor -0.174 Columns Gene: gene name Transcript: transcript ID Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor Coefficient: value of the regression coefficient. The intercept value is -1.3719. CRC+BRCA model Feature Gene Transcript Region Group Coefficient 1 SLC11A1 ENST00000465984 promoter blood 0.150 2 NLRP12 ENST00000324134 promoter blood 0.181 3 PRTN3 ENST00000234347 promoter blood 0.124 4 HMBS ENST00000392841 promoter blood 0.251 5 LILRB3 ENST00000460208 promoter blood 0.140 6 ACSL1 ENST00000513001 junction blood 0.106 7 GP9 ENST00000307395 junction blood 0.251 8 MX2 ENST00000398632 promoter blood 0.106 9 RASGRP4 ENST00000615340 promoter blood 0.222 10 ATG16L2 ENST00000542481 promoter blood 0.166 Table S5 Observed ctDNA fractions in the LOD analysis for the CRC model. Sample Group Expected ctDNA fraction Observed ctDNA fraction 1279 221015-0.005 positive 0.0050 0.0015 1279_221015-0.010 positive 0.0100 0.0192 1279_221015-0.015 positive 0.0150 0.0170 1279_221015-0.020 positive 0.0200 0.0246 1279_221015-0.025 positive 0.0250 0.0250 1279_221015-0.030 positive 0.0300 0.0389 1279_221015-0.035 positive 0.0350 0.0426 1279_221015-0.040 positive 0.0400 0.0471 1279 .221015-0.045 positive 0.0450 0.0750 1279 .221015-0.050 positive 0.0500 0.0692 1279 .221015-0.075 positive 0.0750 0.0964 1279 .221015-0.100 positive 0.1000 0.1093 1279 .221015-0.125 positive 0.1250 0.1210 1279 .221015-0.150 positive 0.1500 0.1381 1279 .221015-0.175 positive 0.1750 0.1250 1279 .221015-0.200 positive 0.2000 0.1452 1279. .221015-0.225 positive 0.2250 0.1590 1279. .221015-0.250 positive 0.2500 0.2252 1279. .221015-0.275 positive 0.2750 0.2856 1279. .221015-0.300 positive 0.3000 0.3152 1279. .221015-0.325 positive 0.3250 0.3456 1279. .221015-0.350 positive 0.3500 0.3587 1279. .221015-0.375 positive 0.3750 0.3994 1279. .221015-0.400 positive 0.4000 0.4318 1279. .221015-0.425 positive 0.4250 0.4363 1279. .221015-0.450 positive 0.4500 0.4634 1279. .221015-0.475 positive 0.4750 0.4652 1279. .221015-0.500 positive 0.5000 0.4776 1279. .241116-0.005 positive 0.0050 0.0033 1279. .241116-0.010 positive 0.0100 0.0150 1279. .241116-0.015 positive 0.0150 0.0420 1279. .241116-0.020 positive 0.0200 0.0368 1279. .241116-0.025 positive 0.0250 0.0396 1279. .241116-0.030 positive 0.0300 0.0439 1279. .241116-0.035 positive 0.0350 0.0439 1279. .241116-0.040 positive 0.0400 0.0576 1279. .241116-0.045 positive 0.0450 0.0574 1279. .241116-0.050 positive 0.0500 0.0692 1279. .241116-0.075 positive 0.0750 0.0508 1279. .241116-0.100 positive 0.1000 0.0707 1279. .241116-0.125 positive 0.1250 0.1357 1279. .241116-0.150 positive 0.1500 0.1457 1279. .241116-0.175 positive 0.1750 0.1366 1279. .241116-0.200 positive 0.2000 0.1632 1279. .241116-0.225 positive 0.2250 0.2000 1279. .241116-0.250 positive 0.2500 0.2310 1279. .241116 0.275 positive 0.2750 0.2914 1279. .241116-0.300 positive 0.3000 0.3281 1279. .241116-0.325 positive 0.3250 0.3622 1279. .241116-0.350 positive 0.3500 0.3690 1279. .241116-0.375 positive 0.3750 0.3762 1279. .241116-0.400 positive 0.4000 0.4185 1279. .241116-0.425 positive 0.4250 0.4311 1279. .241116-0.450 positive 0.4500 0.4618 1279. .241116-0.475 positive 0.4750 0.4958 1279. .241116-0.490 positive 0.4900 0.4937 512_ 051015-0.005 positive 0.0050 0.0049 512_051015-0.010 positive 0.0100 0.0077 512 051015-0.015 positive 0.0150 0.0133 512_051015-0.020 positive 0.0200 0.0163 512_051015-0.025 positive 0.0250 0.0235 512_051015-0.030 positive 0.0300 0.0311 512_051015-0.035 positive 0.0350 0.0322 512_051015-0.040 positive 0.0400 0.0330 512_051015-0.045 positive 0.0450 0.0371 512_051015-0.050 positive 0.0500 0.0296 512_051015-0.075 positive 0.0750 0.0388 512_051015-0.100 positive 0.1000 0.0500 512_051015-0.125 positive 0.1250 0.0682 512_051015-0.150 positive 0.1500 0.0881 512_051015-0.175 positive 0.1750 0.0743 512_051015-0.200 positive 0.2000 0.0948 512_051015-0.225 positive 0.2250 0.1386 512_051015-0.250 positive 0.2500 0.1762 512_051015-0.275 positive 0.2750 0.2095 512_051015-0.300 positive 0.3000 0.2319 51 2051 015-0.325 positive 0.3250 0.2451 512_051015-0.350 positive 0.3500 0.2761 512_051015-0.375 positive 0.3750 0.2971 512_051015-0.400 positive 0.4000 0.3063 512_051015-0.425 positive 0.4250 0.3056 512_051015-0.450 positive 0.4500 0.3568 512_051015-0.475 positive 0.4750 0.4021 512_051015-0.500 positive 0.5000 0.4009 512_051015-0.525 positive 0.5250 0.4008 512_051015-0.550 positive 0.5500 0.4460 512_051015-0.575 positive 0.5750 0.4464 512_051015-0.600 positive 0.6000 0.4736 512_051015-0.614 positive 0.6140 0.4474 512_130114-0.005 positive 0.0050 0.0136 512_130114-0.010 positive 0.0100 0.0167 512_130114-0.015 positive 0.0150 0.0198 512_130114-0.020 positive 0.0200 0.0363 512_130114-0.025 positive 0.0250 0.0352 512_130114-0.030 positive 0.0300 0.0402 512_130114 0.035 positive 0.0350 0.0285 512_130114-0.040 positive 0.0400 0.0309 512_130114-0.045 positive 0.0450 0.0374 512_130114-0.050 positive 0.0500 0.0406 512_130114-0.075 positive 0.0750 0.0492 512_130114-0.100 positive 0.1000 0.0904 512_130114-0.125 positive 0.1250 0.1008 512_130114-0.150 positive 0.1500 0.1432 512 130114-0.175 positive 0.1750 0.2025 512_130114-0.200 positive 0.2000 0.2242 512_130114-0.225 positive 0.2250 0.2376 512_130114-0.250 positive 0.2500 0.2570 512_130114-0.275 positive 0.2750 0.3262 512_130114-0.300 positive 0.3000 0.3659 512_130114-0.325 positive 0.3250 0.3947 512_130114-0.350 positive 0.3500 0.4564 512_130114-0.375 positive 0.3750 0.4838 512_130114-0.394 positive 0.3940 0.4822 sub-healthy-1 negative 0.0000 0.0000 sub-healthy-2 negative 0.0000 0.0024 sub-healthy-3 negative 0.0000 0.0001 sub-healthy-4 negative 0.0000 0.0005 sub-healthy-5 negative 0.0000 0.0000 sub-healthy-6 negative 0.0000 0.0162 sub-healthy-7 negative 0.0000 0.0065 sub-healthy-8 negative 0.0000 0.0000 sub-healthy-9 negative 0.0000 0.0084 sub-healthy-10 negative 0.0000 0.0071 sub-healthy-11 negative 0.0000 0.0000 sub-healthy-12 negative 0.0000 0.0124 sub-healthy-13 negative 0.0000 0.0013 sub-healthy-14 negative 0.0000 0.0118 sub-healthy-15 negative 0.0000 0.0109 sub-healthy-16 negative 0.0000 0.0069 sub-healthy-17 negative 0.0000 0.0116 sub-healthy-18 negative 0.0000 0.0076 sub-healthy-19 negative 0.0000 0.0049 sub-healthy-20 negative 0.0000 0.0000 sub-healthy-21 negative 0.0000 0.0000 sub-healthy-22 negative 0.0000 0.0095 sub-healthy-23 negative 0.0000 0.0106 sub-healthy-24 negative 0.0000 0.0121 sub-healthy-25 negative 0.0000 0.0085 sub-healthy-26 negative 0.0000 0.0000 sub-healthy-27 negative 0.0000 0.0176 sub-healthy-28 negative 0.0000 0.0099 sub-healthy-29 negative 0.0000 0.0000 sub-healthy-30 negative 0.0000 0.0076 sub-healthy-31 negative 0.0000 0.0002 sub-healthy-32 negative 0.0000 0.0076 sub-healthy-33 negative 0.0000 0.0078 sub-healthy-34 negative 0.0000 0.0071 sub-healthy-35 negative 0.0000 0.0077 sub-healthy-36 negative 0.0000 0.0110 sub-healthy-37 negative 0.0000 0.0074 sub-healthy-38 negative 0.0000 0.0000 sub-healthy-39 negative 0.0000 0.0000 sub-healthy-40 negative 0.0000 0.0105

TABLE S6 CRC plasma samples for Ip-WGS and targeted sequencing. icharCNA- NDR- sample patient sample cancer Ip-WGS estimated estimated name ID ID type coverage ctDNA content max VAF ctDNA content 069_020913 69 CRC-13 CRC 1.97 0.00 undetected 0.00 069_310316 69 CRC-14 CRC 7.01 0.09 undetected 0.08 095_100913 95 CRC-15 CRC 5.77 0.38 0.54 0.37 095_150513 95 CRC-16 CRC 6.18 0.43 0.55 0.47 1014_140616 1014 CRC-17 CRC 1.82 0.39 0.56 0.38 1176_040815 1176 CRC-18 CRC 2.96 0.05 undetected 0.21 1176_111116 1176 CRC-19 CRC 1.35 0.00 undetected 0.06 1176_240715 1176 CRC-20 CRC 1.27 0.00 0.11 0.06 1179_160316 1179 CRC-21 CRC 1.96 0.16 0.29 0.25 1179_270715 1179 CRC-22 CRC 3.78 0.18 0.20 0.34 1429_141116 1429 CRC-23 CRC 0.42 0.20 undetected 0.08 1429_170316 1429 CRC-24 CRC 5.83 0.39 0.36 0.36 1490_050516 1490 CRC-25 CRC 2.12 0.49 0.72 0.49 1490_171116 1490 CRC-26 CRC 2.08 0.00 undetected 0.33 149_100613 149 CRC-27 CRC 2.43 0.00 undetected 0.19 149_130214 149 CRC-28 CRC 3.72 0.05 undetected 0.18 1531_010716 1531 CRC-29 CRC 1.38 0.48 0.77 0.49 1531_111016 1531 CRC-30 CRC 4.23 0.00 undetected 0.07 1531_111116 1531 CRC-31 CRC 1.93 0.00 undetected 0.00 330_091115 330 CRC-32 CRC 5.93 0.23 0.38 0.25 330_170414 330 CRC-33 CRC 6.93 0.00 undetected 0.00 357_110716 357 CRC-34 CRC 3.48 0.51 0.56 0.49 357_230913 357 CRC-35 CRC 2.06 0.00 undetected 0.11 357_290216 357 CRC-36 CRC 4.28 0.57 0.49 0.39 357_291015 357 CRC-37 CRC 5.94 0.37 0.29 0.38 375_021116 375 CRC-38 CRC 3.13 0.00 undetected 0.10 375_210115 375 CRC-39 CRC 2.90 0.00 undetected 0.17 386_091214 386 CRC-40 CRC 0.70 0.09 0.22 0.21 386_180516 386 CRC-41 CRC 3.86 0.32 0.49 0.38 476_050916 476 CRC-42 CRC 1.09 0.11 0.19 0.09 476_110315 476 CRC-43 CRC 3.32 0.12 0.27 0.20 519_020715 519 CRC-44 CRC 6.30 0.15 0.17 0.29 519_140116 519 CRC-45 CRC 2.31 0.06 undetected 0.14 519_240314 519 CRC-46 CRC 4.88 0.29 0.51 0.33 571_261114 571 CRC-47 CRC 2.64 0.00 undetected 0.06 571_291015 571 CRC-48 CRC 2.07 0.05 undetected 0.15 575_191015 575 CRC-49 CRC 2.63 0.11 0.12 0.10 575_270214 575 CRC-50 CRC 1.40 0.19 0.11 0.18 575_270516 575 CRC-51 CRC 2.13 0.00 0.11 0.11 575_270616 575 CRC-52 CRC 6.88 0.05 undetected 0.21 592_171116 592 CRC-53 CRC 2.42 0.00 undetected 0.08 592_280316 592 CRC-54 CRC 3.01 0.00 undetected 0.09 741_091116 741 CRC-55 CRC 1.50 0.00 undetected 0.07 741_150415 741 CRC-56 CRC 4.26 0.00 undetected 0.10 834_090715 834 CRC-57 CRC 2.71 0.00 undetected 0.00 834_241116 834 CRC-58 CRC 4.41 0.13 undetected 0.09 836_090415 836 CRC-59 CRC 1.27 0.00 undetected 0.04 836_090715 836 CRC-60 CRC 4.39 0.00 undetected 0.17 836_180416 836 CRC-61 CRC 4.23 0.39 0.25 0.22 897_200815 897 CRC-62 CRC 6.55 0.34 0.47 0.26 897_220316 897 CRC-63 CRC 8.03 0.07 0.16 0.07 986_060315 986 CRC-64 CRC 6.37 0.19 0.19 0.31 986_260916 986 CRC-65 CRC 4.52 0.28 0.73 0.47

TABLE S7 A panel of 100 genes frequently mutated in colorectal and breast cancer. ABL1 ACVR2A AKT1 ALK APC ARID1A ATM ATR AURKA B2M BCL9L BRAF BRCA1 BRCA2 CALR CANX CDH1 CDKN1B CDKN2A CHD4 CSF1R CTCF CTNNB1 DCC DDR2 DMD DOT1L EGFR EP300 ERBB2 ERBB3 ERBB4 ESR1 EZH2 FBXW7 FGFR1 FGFR2 FGFR3 FLT3 GATA3 GNA11 GNAQ GNAS HLA-A HNF1A HRAS HSPA5 IDH1 IDH2 JAK1 JAK2 JAK3 KDR KIT KMT2C KRAS MAGI3 MAP2K1 MAP2K4 MAP3K1 MDM2 MDM4 MET MLH1 MPL MTOR MUC17 NF1 NOTCH1 NOTCH4 NPM1 NRAS PDGFRA PDIA3 PIK3CA PIK3R1 POLD1 POLD2 POLE PTEN PTPN11 RB1 RBM10 RET RNF43 SMAD2 SMAD4 SMARCB1 SMO SOX9 SRC STK11 TAP1 TAPBP TP53 TSC1 TSC2 VHL ZFP36L2 ZNRF3

TABLE S8 Variant allele frequency estimation of CRC plasma samples. Pos Sample Chr (GRCh38) Ref Alt Codon AA Gene T095_100913 chr12 25245350 C T gGt/gAt G/D ENSG00000133703 T095_100913 chr17 72124084 — +C —/C —/X ENSG00000125398 T095_100913 chr17 7674230 C T Ggc/Agc G/S ENSG00000141510 T095_150513 chr12 25245350 C T gGt/gAt G/D ENSG00000133703 T095_150513 chr17 72124084 — +C —/C —/X ENSG00000125398 T095_150513 chr17 7674230 C T Ggc/Agc G/S ENSG00000141510 T1014_110115 chr2 147926116- — −A Aaa/aa K/X ENSG00000121989 7 T1014_140616 chr14 104773077 C A Gac/Tac D/Y ENSG00000142208 T1014_140616 chr17 72122793 A T cAc/cTc H/L ENSG00000125398 T1014_140616 chr5 112839783 G T Gag/Tag E/* ENSG00000134982 T1014_180816 chr14 104773077 C A Gac/Tac D/Y ENSG00000142208 T1014_180816 chr17 72122793 A T cAc/cTc H/L ENSG00000125398 T1014_180816 chr5 112839783 G T Gag/Tag E/* ENSG00000134982 T1176_240715 chr3 142555897- — −T Ata/ta I/X ENSG00000175054 8 T1179_160316 chr12 25245351 C A Ggt/Tgt G/C ENSG00000133703 T1179_160316 chr17 7674250 C A tGt/tTt C/F ENSG00000141510 T1179_160316 chr4 152329715 G T tCt/At S/Y ENSG00000109670 T1179_160316 chr5 112839826- — −T agT/ag S/X ENSG00000134982 7 T1179_270715 chr12 25245351 C A Ggt/Tgt G/C ENSG00000133703 T1179_270715 chr17 7674250 C A tGt/tTt C/F ENSG00000141510 T1179_270715 chr5 112839826- — −T agT/ag S/X ENSG00000134982 7 T1279_221015 chr10 87933148 G A cGa/cAa R/Q ENSG00000171862 T1279_221015 chr6 112839240 G T Gag/Tag E/* ENSG00000134982 T1279_241116 chr10 87933148 G A cGa/cAa R/Q ENSG00000171862 T1279_241116 chr5 112839240 G T Gag/Tag E/* ENSG00000134982 T1429_141116 chr1 114716126 C T gGt/gAt G/D ENSG00000213281 T1429_141116 chr11 108297326 A G aAt/aGt N/S ENSG00000149311 T1429_141116 chr12 132641691 G A gcC/gcT A ENSG00000177084 T1429_141116 chr12 6581743 C T aaG/aaA K ENSG00000111642 T1429_141116 chr13 32332343 A C Aat/Cat N/H ENSG00000139618 T1429_141116 chr13 32332843 A G tcA/tcG S ENSG00000139618 T1429_141116 chr13 32336584 T C caT/caC H ENSG00000139618 T1429_141116 chr13 32337326 A G Aac/Gac N/D ENSG00000139618 T1429_141116 chr17 43071077 T C Agt/Ggt S/G ENSG00000012048 T1429_141116 chr17 43082453 A G tcT/tcC S ENSG00000012048 T1429_141116 chr17 43091983 T C aAa/aGa K/R ENSG00000012048 T1429_141116 chr17 43092418 T C gAa/gGa E/G ENSG00000012048 T1429_141116 chr17 43093220 A G Ttg/Ctg L ENSG00000012048 T1429_141116 chr17 43093449 G A agC/agT S ENSG00000012048 T1429_141116 chr17 58362569 C T cGg/cAg R/Q ENSG00000108375 T1429_141116 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T1429_141116 chr4 54736599 G C ctG/ctC L ENSG00000157404 T1429_141116 chr4 55113321 G A aCa/aTa T/I ENSG00000128052 T1429_141116 chr6 32221046 G A tCg/tTg S/L ENSG00000204301 T1429_141116 chr6 32847198 T C gAt/gGc D/G ENSG00000168394 T1429_170316 chr1 114713908 T A cAa/cTa Q/L ENSG00000213281 T1429_170316 chr10 8058488 C T tCg/tTg S/L ENSG00000107485 T1429_170316 chr16 68815631 T C gaT/gaC D ENSG00000039068 T1429_170316 chr17 7674230 C T Ggc/Agc G/S ENSG00000141510 T1429_170316 chr22 29049985 C T Cgg/Tgg R/W ENSG00000183579 T1429_170316 chr5 112792446 C T Cga/Tga R/* ENSG00000134982 T1490_050516 chr1 11240392 G A gCc/gTc A/V ENSG00000198793 T1490_050516 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T1490_050516 chr19 2226938 C T Cag/Tag Q/* ENSG00000104885 T1490_050516 chr4 55118645 C T cGg/cAg R/Q ENSG00000128052 T1490_050516 chr5 112838070 — +TGAATACTACA ttg/tTGAATACTACAtg L/LNTTX ENSG00000134982 T1490_050516 chr5 112839474 C T Cag/Tag Q/* ENSG00000134982 T1531_010716 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T1531_010716 chr2 43224452 T G gAc/gCc D/A ENSG00000152518 T1531_010716 chr5 112839439 C A tCa/tAa S/* ENSG00000134982 T1531_160616 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T1531_160616 chr5 112839439 C A tCa/tAa S/* ENSG00000134982 T330_091115 chr11 118908483 — +G —/C —/X ENSG00000186174 T330_091115 chr19 50409156 G A Gcg/Agc G/R ENSG00000062822 T330_091115 chr4 152326137 G A Cgc/Tgc R/C ENSG00000109670 T330_091115 chr5 112839576 C T Cag/Tag Q/* ENSG00000134S82 T330_091115 chr5 150089316 C T Gtg/Atg V/M ENSG00000182578 T357_110716 chr12 25245350 C T gGt/gAt G/D ENSG00000133703 T357_110716 chr13 32362670 G T agG/agT R/S ENSG00000139618 T357_110716 chr17 7674945 G A Cga/Tga R/* ENSG00000141510 T357_110716 chr2 211657762 T G caA/caC Q/H ENSG00000178568 T357_110716 chr2 43224819- — −CGCGGCCGCCGCGGAGG gCCTCCGCGGCGGCCGCG/g ASAAAA/X ENSG00000152518 36 T357_290216 chr12 25245350 C T gCt/gAt G/D ENSG00000133703 T357_290216 chr13 32362670 G T agG/agT R/S ENSG00000139618 T357_290216 chr17 7674945 G A Cga/Tga R/* ENSG00000141510 T357_290216 chr2 211657762 T G caA/caC Q/H ENSG00000178568 T357_290216 chr2 43224819- — −CGCGGCCGCCGCGGAGG gCCTCCGCGGCGGCCGCG/g ASAAAA/X ENSG00000152518 36 T357_291015 chr12 25245350 G T gGt/gAt G/D ENSG00000133703 T357_291015 chr13 32362670 G T agG/agT R/S ENSG00000139618 T357_291015 chr17 7574945 G A Cga/Tga R/* ENSG00000141510 T357_291015 chr2 211657762 T G caA/caC Q/H ENSG00000178568 T357_291015 chr2 43224819- — −CGCGGCCGCCGCGGAGG gCCTCCGCGGCGGCCGCG/g ASAAAA/X ENSG00000152518 36 T386_091214 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T386_091214 chr3 179218307 A C cAg/cCg Q/P ENSG00000121879 T386_091214 chr5 112837893 C T Cag/Tag Q/* ENSG00000134982 T386_091214 chrX 33020185 A G gTt/gCt V/A ENSG00000198947 T386_180516 chr10 121503937 G C tCg/tGg S/W ENSG00000066468 T386_180516 chr12 112504716 A T agA/agT R/S ENSG00000179295 T386_180516 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T386_180516 chr3 179218307 A C cAg/cCg Q/P ENSG00000121879 T386_180516 chr5 112837893 C T Cag/Tag Q/* ENSG00000134982 T386_180516 chr5 112839543 G T Gaa/Taa E/* ENSG00000134982 T386_180516 chr8 38421931 A T gTt/gAt V/D ENSG00000077782 T386_180516 chrX 33020185 A G gTt/gCt V/A ENSG00000198947 T476_050916 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T476_050916 chr2 43225692 — +C —/G —/X ENSG00000152518 T476_110315 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T476_110315 chr2 43225692 — +C —/G —/X ENSG00000152518 T476_110315 chr3 179221102 A T aAg/aTg K/M ENSG00000121879 T512_051015 chr15 43768557 A C aAg/aCg K/T ENSG00000167004 T512_051015 chr18 51065534 C T cCt/cTt P/L ENSG00000141646 T512_051015 chr5 112839729 G T Gag/Tag E/* ENSG00000134982 T512_130114 chr18 51065534 C T cCt/cTt P/L ENSG00000141646 T512_130114 chr5 112839729 G T Gag/Tag E/* ENSG00000134982 T519_020715 chr17 7673803 G A Cgt/Tgt R/C ENSG00000141510 T519_210114 chr17 7673803 G A Cgt/Tgt R/C ENSG00000141510 T519_210114 chr20 58903555 C A gaC/gaA D/E ENSG00000087460 T519_210114 chr5 112839465 C T Cag/Tag Q/* ENSG00000134982 T519_210114 chr5 56871965 G T Gaa/Taa E/* ENSG00000095015 T519_240314 chr17 7673803 G A Cgt/Tgt R/C ENSG00000141510 T519_240314 chr20 58903555 C A gaC/gaA D/E ENSG00000087460 T519_240314 chr5 112839465 C T Cag/Tag Q/* ENSG00000134982 T519_240314 chr5 56871965 G T Gaa/Taa E/* ENSG00000095015 T575_191015 chr17 7673811 A G tTt/tCt F/S ENSG00000141510 T575_191015 chr3 142555897- — −T Ata/ta I/X ENSG00000175054 8 T575_270214 chr17 7673811 A G tTt/tCt F/S ENSG00000141510 T575_270516 chr3 142555897- — −T Ata/ta I/K ENSG00000175054 8 T809_030915 chr1 64869346 C A aaG/aaT K/N ENSG00000162434 T809_030915 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T809_030915 chr5 112839693 C T Cag/Tag Q/* ENSG00000134982 T809_110914 chr1 64869346 C A aaG/aaT K/N ENSG00000162434 T809_110914 chr17 7675088 C T cGc/cAc R/H ENSG00000141510 T809_110914 chr5 112839693 C T Cag/Tag Q/* ENSG00000134982 T836_180416 chr17 7674939 C A Gaa/Taa E/* ENSG00000141510 T836_180416 chr5 112839474 C T Cag/Tag Q/* ENSG00000134982 T897_200815 chr12 25245347 C T gGc/gAc G/D ENSG00000133703 T897_200815 chr17 72124097 — +CG tcg/tCGcg S/SX ENSG00000125398 T897_200815 chr17 7675067- — −A Tgc/gc C/X ENSG00000141510 8 T897_200815 chr18 51065549 G A cGc/cAc R/H ENSG00000141646 T897_200815 chr18 51078286 A T gAt/gTt D/V ENSG00000141646 T897_200815 chr22 29050710 C T ccC/ccT P ENSG00000183579 T897_200815 chr3 179199088 G A cGa/cAa R/Q ENSG00000121879 T897_200815 chr4 162329695- — −T aaA/aa K/X ENSG00000109670 8 T897_200815 chr5 112839714 G T Gaa/Taa E/* ENSG00000134982 T897_220316 chr5 112839714 G T Gaa/Taa E/* ENSG00000134982 T986_060315 chr17 7675076 T C cAt/cGt H/R ENSG00000141510 T986_060315 chr3 179218304 A G gAg/gGg E/G ENSG00000121879 T986_060315 chr5 112792446 C T Cga/Tga R/* ENSG00000134982 T986_100215 chr17 7675076 T C cAt/cGt H/R ENSG00000141510 T986_100215 chr3 179218304 A G gAg/gGg E/G ENSG00000121879 T886_100215 chr5 112792446 C T Cga/Tga R/* ENSG00000134982 T986_260916 chr17 72123617 — +GA cga/cGAga R/RX ENSG00000125398 T986_260916 chr17 7675076 T C cA/cGt H/R ENSG00000141510 T986_260916 chr3 179218304 A G gAg/gGg E/G ENSG00000121879 T986_260916 chr5 112792446 C T Cga/Tga R/* ENSG00000134982 T986_261016 chr17 72123617 — +GA cga/cGAga R/RX ENSG00000125398 T986_261016 chr17 7675076 T C cAt/cGt H/R ENSG00000141510 T986_261016 chr3 178218304 A G gAg/gGg E/G ENSG00000121879 T986_261016 chr5 112732446 C T Cga/Tga R/* ENSG00000134982 T986_261016 chr7 55165435 C T taC/taT Y ENSG00000416648 Symbol/ mutect_VAF varscan_VAF mutect_VAF varscan_VAF Sample Gene Feature Exon Tumour Tumour Normal Normal MedianVAF T095_100913 KRAS ENST00000256078 2/6 0.211 0.212 0 0 0.2115 T095_100913 SOX9 ENST00000245479 3/3 0.202 0 0.202 T095_100913 TP53 ENST00000269305  7/11 0.539 0 0.539 T095_150513 KRAS ENST00000256078 2/6 0.234 0.221 0 0 0.2275 T095_150513 SOX9 ENST00000245479 3/3 0.187 0 0.187 T095_150513 TP53 ENST00000269305  7/11 0.553 0 0.553 T1014_110115 ACVR2A ENST00000241416 10/11 0.285 0.006 0.286 T1014_140616 AKT1 ENST00000554581 10/13 0.199 0.199 0 0 0.199 T1014_140616 SOX9 ENST00000245479 2/3 0.367 0 0.367 T1014_140616 ARC ENST00000257430 16/16 0.559 0 0.559 T1014_180816 AKT1 ENST00000554581 10/13 0.246 0.256 0 0 0.251 T1014_180816 SOX9 ENST00000245479 2/3 0.305 0.284 0 0 0.2945 T1014_180816 APC ENST00000257430 16/16 0.458 0.002 0.458 T1176_240715 ATR ENST00000350721 10/47 0.108 0.037 0.108 T1179_160316 KRAS ENST00000256076 2/6 0.289 0.288 0.001 0 0.2885 T1179_160316 TP53 ENST00000269305  7/11 0.275 0.265 0 0.001 0.27 T1179_160316 FBXW7 ENST00000281708  8/12 0.119 0.104 0 0 0.1115 T1179_160316 APC ENST00000257430 16/16 0.241 0.001 0.241 T1179_270715 KRAS ENST00000256078 2/6 0.203 0.198 0.001 0 0.2005 T1179_270715 TP53 ENST00000269305  7/11 0.14 0.143 0 0.001 0.1415 T1179_270715 APC ENST00000257430 16/16 0.185 0.001 0.185 T1279_221015 PTEN ENST00000371953 5/9 0.515 0 0.615 T1279_221015 APC ENST00000257430 16/16 0.54 0.001 0.64 T1279_241116 PTEN ENST00000371953 5/9 0.378 0 0.378 T1279_241116 APC ENST00000257430 16/16 0.447 0.001 0.447 T1429_141116 NRAS ENST00000369535 2/7 0.108 0.135 0 0 0.1215 T1429_141116 ATM ENST00000278616 33/63 0.465 0 0.465 T1429_141116 POLE ENST00000320574 39/49 0.547 0 0.547 T1429_141116 CHD4 ENST00000357008 31/40 0.46 0.001 0.45 T1429_141116 BRCA2 ENST00000380152 10/27 0.403 0 0.403 T1429_141116 BRCA2 ENST00000380152 10/27 0.41 0 0.41 T1429_141116 BRCA2 ENST00000380152 11/27 0.465 0 0.465 T1429_141116 BRCA2 ENST00000380152 11/27 0.451 0 0.451 T1429_141116 BRCA1 ENST00000471181 16/24 0.521 0.001 0.621 T1429_141116 BRCA1 ENST00000471181 12/24 0.456 0 0.456 T1429_141116 BRCA1 ENST00000471181 10/24 0.495 0.001 0.495 T1429_141116 BRCA1 ENST00000471181 10/24 0.461 0.002 0.461 T1429_141116 BRCA1 ENST00000471181 10/24 0.489 0.001 0.489 T1429_141116 BRCA1 ENST00000471181 10/24 0.483 0.001 0.483 T1429_141116 RNF43 ENST00000584437 5/9 0.435 0.001 0.435 T1429_141116 TP53 ENST00000269305  5/11 0.109 0.001 0.109 T1429_141116 KIT ENST00000288135 18/21 0.443 0 0.443 T1429_141116 KDR ENST00000263923  7/30 0.479 0 0.479 T1429_141116 NOTCH4 ENST00000375023  4/30 0.35 0.341 0 0 0.3455 T1429_141116 TAP1 ENST00000354258 10/11 0.661 0.001 0.661 T1429_170316 NRAS ENST00000369535 3/7 0.348 0.322 0 0 0.335 T1429_170316 GATA3 ENST00000379328 3/6 0.2 0.199 0 0 0.1995 T1429_170316 CDH1 ENST00000261769 10/16 0.357 0.001 0.357 T1429_170316 TP53 ENST00000269305  7/11 0.345 0.341 0 0 0.343 T1429_170316 ZNRF3 ENST00000544604 8/9 0.233 0.232 0 0.001 0.2325 T1429_170316 APC ENST00000267430  7/16 0.268 0.231 0 0 0.2495 T1490_050516 MTOR ENST00000361445 11/58 0.164 0.145 0 0 0.1545 T1490_050516 TP53 ENST00000269305  5/11 0.719 0 0.719 T1490_050516 DOT1L ENST00000398665 27/28 0.24 0.267 0.001 0 0.2535 T1490_050516 KDR ENST00000263923  3/30 0.362 0 0.362 T1490_050516 APC ENST00000257430 16/16 0.185 0 0.185 T1490_050516 APC ENST00000257430 16/16 0.526 0 0.526 T1531_010716 TP53 ENST00000269305  5/11 0.747 0.001 0.747 T1531_010716 ZFP36L2 ENST00000282388 2/2 0.309 0 0.309 T1531_010716 APC ENST00000257430 16/16 0.77 0 0.77 T1531_160616 TP53 ENST00000269305  6/11 0.788 0 0.788 T1531_160616 APC ENST00000257430 16/16 0.79 0 0.79 T330_091115 BCL9L ENST00000334801 2/8 0.224 0 0.224 T330_091115 POLD1 ENST00000440232 16/27 0.259 0.256 0 0 0.2575 T330_091115 FBXW7 ENST00000281708 10/12 0.382 0 0.382 T330_091115 APC ENST00000267430 16/16 0.366 0 0.366 T330_091115 CSF1R ENST00000286301  4/22 0.169 0.161 0.001 0 0.165 T357_110716 KRAS ENST00000256078 2/6 0.496 0 0.496 T357_110716 BRCA2 ENST00000380152 17/27 0.233 0.256 0 0 0.2445 T357_110716 TP53 ENST00000269305  6/11 0.56 0 0.56 T357_110716 ER884 ENST00000342788 16/28 0.172 0.001 0.172 T357_110716 ZFP36L2 ENST00000282388 2/2 0.324 0.001 0.324 T357_290216 KRAS ENST00000256078 2/6 0.494 0 0.494 T357_290216 BRCA2 ENST00000380152 17/27 0.181 0.174 0 0 0.1775 T357_290216 TP53 ENST00000269305  6/11 0.488 0 0.488 T357_290216 ER884 ENST00000342788 16/28 0.142 0.001 0.142 T357_290216 2FP36L2 ENST00000282388 2/2 0.271 0.001 0.271 T357_291015 KRAS ENST00000256078 2/6 0.291 0.297 0 0 0.294 T357_291015 BRCA2 ENST00000360152 17/27 0.132 0.135 0 0 0.1335 T357_291015 TP53 ENST00000269305  6/11 0.247 0.248 0 0 0.2475 T357_291015 ER884 ENST00000342788 16/28 0.106 0.001 0.106 T357_291015 ZFP36L2 ENST00000282388 2/2 0.17 0.001 0.17 T386_091214 TP53 ENST00000269305  5/11 0.228 0.218 0.001 0.001 0.223 T386_091214 PIK3CA ENST00000263967 10/21 0.154 0.15 0.001 0.001 0.152 T386_091214 APC ENST00000257430 16/16 0.111 0.11 0.001 0 0.1105 T386_091214 DMD ENST00000357033  2/79 0.11 0.113 0 0 0.1115 T386_180516 FGFR2 ENST00000457416 10/18 0.135 0.177 0 0 0.156 T386_180516 PTPN11 ENST00000351677 15/16 0.223 0.236 0 0 0.2295 T386_180516 TP53 ENST00000269305  5/11 0.484 0.001 0.494 T386_180516 PIK3CA ENST00000263967 10/21 0.384 0.001 0.384 T386_180516 APC ENST00000257430 16/16 0.292 0.288 0.001 0 0.29 T386_180516 APC ENST00000257430 16/16 0.23 0.244 0 0 0.237 T386_180516 FGFR1 ENST00000425967  9/19 0.188 0.192 0 0 0.19 T386_180516 DMD ENST00000357033  2/79 0.274 0.308 0 0 0.291 T476_050916 TP53 ENST00000269305  5/11 0.183 0.195 0 0.001 0.189 T476_050916 ZFP36L2 ENST00000282388 2/2 0.176 0 0.176 T476_110315 TP53 ENST00000269305  5/11 0.243 0.264 0 0.001 0.2535 T476_110315 ZFP36L2 ENST00000282388 2/2 0.272 0 0.272 T476_110315 PIK3CA ENST00000263967 14/21 0.12 0.113 0 0 0.1165 T512_051015 PDIA3 ENST00000300289  9/13 0.095 0.104 0 0 0.0995 T512_051015 SMAD4 ENST00000342988  9/12 0.614 0 0.614 T512_051015 APC ENST00000257430 16/16 0.684 0 0.684 T512_130114 SMAD4 ENST00000342988  9/12 0.371 0 0.371 T512_130114 APC ENST00000257430 16/16 0.464 0 0.464 T519_020715 TP53 ENST00000269305  8/11 0.173 0.166 0 0 0.1695 T519_210114 TP53 ENST00000269305  8/11 0.43 0 0.43 T519_210114 GNAS ENST00000371100  4/13 0.111 0.12 0 0 0.1155 T519_210114 APC ENST00000257430 16/16 0.195 0.189 0 0.001 0.192 T519_210114 MAP3K1 ENST00000399503  7/20 0.192 0.194 0 0 0.193 T519_240314 TP53 ENST00000269305  8/11 0.513 0 0.613 T519_240314 GNAS ENST00000371100  4/13 0.12 0.109 0 0 0.1145 T519_240314 APC ENST00000257430 16/16 0.215 0.223 0 0.001 0.219 T519_240314 MAP3K1 ENST00000399503  7/20 0.205 0.206 0 0 0.205 T575_191015 TP53 ENST00000269305  8/11 0.104 0.103 0.001 0 0.1035 T575_191015 ATR ENST00000350721 10/47 0.116 0.028 0.116 T575_270214 TP53 ENST00000269305  8/11 0.109 0.107 0.001 0 0.108 T575_270516 ATR ENST00000359721 10/47 0.109 0.028 0.109 T809_030915 JAK1 ENST00000342505  6/25 0.123 0.135 0 0 0.129 T809_030915 TP53 ENST00000269305  5/11 0.544 0 0.544 T809_030915 APC ENST00000257430 16/16 0.542 0.001 0.542 T809_110914 JAK1 ENST00000342505  5/25 0.186 0.172 0 0 0.179 T809_110914 TP53 ENST00000269305  5/11 0.727 0 0.727 T809_110914 APC ENST00000257430 16/16 0.744 0.001 0.744 T836_180416 TP53 ENST00000269305  6/11 0.224 0.222 0 0 0.223 T836_180416 APC ENST00000257430 16/16 0.248 0.259 0 0 0.2535 T897_200815 KRAS ENST00000256078 2/6 0.171 0.17 0 0 0.1705 T897_200815 SOX9 ENST00000245479 3/3 0.213 0 0.213 T897_200815 TP53 ENST00000269305  5/11 0.327 0.001 0.327 T897_200815 SMAD4 ENST00000342988  9/12 0.128 0.116 0 0.001 0.122 T897_200815 SMAD4 ENST00000342988 12/12 0.236 0.229 0.001 0 0.2325 T897_200815 ZNRF3 ENST00000544604 8/9 0.204 0.229 0 0 0.2165 T897_200815 PIK3CA ENST00000263967  2/21 0.286 0.304 0 0.001 0.296 T897_200815 FBXW7 ENST00000281708  8/12 0.214 0 0.214 T897_200815 APC ENST00000257430 16/16 0.467 0 0.467 T897_220316 APC ENST00000257430 16/16 0.173 0.156 0 0.001 0.1646 T986_060315 TP53 ENST00000269305  5/11 0.189 0.198 0.001 0.001 0.1936 T986_060315 PIK3CA ENST00000263967 10/21 0.164 0.186 0 0 0.175 T986_060315 APC ENST00000257430  7/16 0.102 0.107 0 0.001 0.1046 T986_100215 TP53 ENST00000269306  5/11 0.306 0.316 0.001 0.001 0.31 T986_100215 PIK3CA ENST00000263967 10/21 0.232 0.222 0 0 0.227 T886_100215 APC ENST00000257430  7/16 0.179 0.174 0 0.001 0.1765 T986_260916 SOX9 ENST00000245479 3/3 0.311 0.001 0.311 T986_260916 TP53 ENST00000269305  5/11 0.726 0.001 0.726 T986_260916 PIK3CA ENST00000263967 10/21 0.65 0 0.65 T986_260916 APC ENST00000257430  7/16 0.559 0 0.569 T986_261016 SOX9 ENST00000245479 3/3 0.206 0.001 0.208 T986_261016 TP53 ENST00000269305  5/11 0.413 0.001 0.413 T986_261016 PIK3CA ENST00000263967 10/21 0.361 0 0.351 T986_261016 APC ENST00000257430  7/16 0.261 0.268 0 0.001 0.2645 T986_261016 EGFR ENST00000275493 15/28 0.164 0.164 0 0 0.1625

TABLE S9 Mutations missed by the callers for the CRC patients with serial plasma samples. ctDNA ctDNA Pos Symbol/ VAF- VAF- VAF- detection - detection - Patient Sample Day chr (GRCh38) Ref Alt Gene Mutect Varscan manual ichorCNA NDR 357 357_230913 34 chr13 32362670 G T BRCA2 undetected undetected 0 negative positive chr2 211657762 T G ERB84 undetected undetected 0 chr12 25245350 C T KRAS undetected undetected 0.0105 chr17 7674945 G A TP53 undetected undetected 0 chr2 43224819-36 — — ZFP36L2 undetected undetected 0 CGCGGC CGCCGC GGAGG 1531 1531_111016  160 chr5 112839439 C A APC undetected undetected 0 negative positive chr17 7675088 C T TP53 undetected undetected 0.0012 1531 1531_111116  191 chr5 112839439 C A APC undetected undetected 0 negative negative chr17 7675088 C T TP53 undetected undetected 0 575 575_270616 864 chr3 142555897-8  — −T ATR undetected undetected 0.0579 positive positive chr17 7673811 A G TP53 undetected undetected 0.0546 519 519_140116 726 chr5 112839465 C T APC undetected undetected 0.0247 positive positive chr20 58903555 C A GNAS undetected undetected 0.0232 chr5 56871965 G T MAP3K1 undetected undetected 0.0177 chr17 7673803 G A TP53 undetected undetected 0.0448

TABLE S10 Information on all candidate pan-cancer features of nucleosome-depleted regions. ID Transcript Gene Chr Site Region Group FPKM_(blood) 1 ENST00000008938.4 PGLYRP1 19 46526323 promoter blood 148.76 2 ENST00000177694.1 TBX21 17 45810610 promoter blood 5.98 3 ENST00000194097.8 NAIP 5 70316737 promoter blood 10.22 4 ENST00000199708.2 HBQ1 16 230452 promoter blood 45.79 5 ENST00000217133.1 TUBB1 20 57594309 promoter blood 6.01 6 ENST00000219596.5 MEFV 16 3306627 promoter blood 19.19 7 ENST00000221804.4 CLC 19 40228668 promoter blood 19.65 8 ENST00000221954.6 CEACAM4 19 42133442 promoter blood 32.81 9 ENST00000225275.3 MPO 17 56358296 promoter blood 7.23 10 ENST00000233997.3 AZU1 19 827836 promoter blood 14.03 11 ENST00000234347.9 PRTN3 19 840960 promoter blood 13.78 12 ENST00000236826.7 MMP8 11 102595685 promoter blood 20.68 13 ENST00000245620.13 LILRB3 19 54726850 promoter blood 22.83 14 ENST00000258104.7 DYSF 2 71680852 promoter blood 6.76 15 ENST00000262407.5 ITGA2B 17 42466873 promoter blood 12.34 16 ENST00000262651.3 HCK 20 30640045 promoter blood 8.74 17 ENST00000262865.8 BPI 20 36932525 promoter blood 18.06 18 ENST00000263621.1 ELANE 19 852291 promoter blood 21.67 19 ENST00000264260.6 IL18RAP 2 103035149 promoter blood 42.11 20 ENST00000264834.4 KLF1 19 12997995 promoter blood 8.95 21 ENST00000267396.8 REM2 14 23352374 promoter blood 6.91 22 ENST00000287497.12 ITGAM 16 31271311 promoter blood 6.52 23 ENST00000294800.7 FCGR3B 1 161601252 promoter blood 13.85 24 ENST00000295619.3 PROK2 3 71834212 promoter blood 12.98 25 ENST00000295683.2 CXCR1 2 219031718 promoter blood 355.57 26 ENST00000296028.3 PPBP 4 74853914 promoter blood 50.15 27 ENST00000296435.2 CAMP 3 48264837 promoter blood 27.17 28 ENST00000297435.2 DEFA4 8 6795860 promoter blood 34.98 29 ENST00000299663.7 CLEC4E 12 8693559 promoter blood 29.27 30 ENST00000299665.2 CLEC4D 12 8666136 promoter blood 10.47 31 ENST00000302312.8 AHSP 16 31539185 promoter blood 85.51 32 ENST00000304076.6 VAV1 19 6772725 promoter blood 7.61 33 ENST00000304361.8 CLEC12A 12 10124014 promoter blood 10.23 34 ENST00000307395.4 GP9 3 128779610 promoter blood 9.72 35 ENST00000307564.8 AKNA 9 117156685 promoter blood 11.95 36 ENST00000310544.8 PHOSPHO1 17 47307890 promoter blood 30.92 37 ENST00000312156.8 NFE2 12 54689544 promoter blood 11.15 38 ENST00000314412.6 FUT7 9 139927462 promoter blood 16.90 39 ENST00000314446.9 LILRB2 19 54785039 promoter blood 7.87 40 ENST00000318507.6 CXCR2 2 218990727 promoter blood 157.27 41 ENST00000324134.10 NLRP12 19 54327597 promoter blood 9.17 42 ENST00000326965.6 TAGAP 6 159466184 promoter blood 5.94 43 ENST00000327857.6 DEFA3 8 6875823 promoter blood 355.10 44 ENST00000329800.7 TMCC2 1 205225329 promoter blood 10.64 45 ENST00000330597.3 HBG1 11 5271122 promoter blood 5.07 46 ENST00000330807.9 ALAS2 X 55057497 promoter blood 142.66 47 ENST00000331941.6 CSF3R 1 36945120 promoter blood 16.12 48 ENST00000335854.8 ALAS2 X 55057410 promoter blood 101.19 49 ENST00000336906.4 HBG2 11 5276041 promoter blood 104.85 50 ENST00000338372.6 VSTM1 19 54567207 promoter blood 10.71 51 ENST00000340023.6 FPR2 19 52264104 promoter blood 34.71 52 ENST00000342063.4 C19orf35 19 2282175 promoter blood 8.64 53 ENST00000342571.7 MKNK1 1 47051643 promoter blood 14.42 54 ENST00000344138.8 GRAP2 22 40297086 promoter blood 5.60 55 ENST00000348343.10 BMX X 15518952 promoter blood 6.99 56 ENST00000353065.7 PROK2 3 71834357 promoter blood 82.89 57 ENST00000355524.7 FCAR 19 55385736 promoter blood 53.04 58 ENST00000356815.3 HBM 16 215977 promoter blood 163.82 59 ENST00000357396.7 CEACAM3 19 42300369 promoter blood 16.26 60 ENST00000367053.5 CR1 1 207669502 promoter blood 10.47 61 ENST00000367964.6 FCGR3B 1 161601753 promoter blood 465.71 62 ENST00000368034.8 CD244 1 160832645 promoter blood 6.27 63 ENST00000373103.5 CSF3R 1 36948879 promoter blood 61.20 64 ENST00000375448.4 PADI4 1 17634692 promoter blood 95.04 65 ENST00000375809.7 C6orf25 6 31691150 promoter blood 5.36 66 ENST00000375862.6 HCK 20 30640000 promoter blood 20.11 67 ENST00000376092.7 LST1 6 31554977 promoter blood 5.01 68 ENST00000376670.7 GATA1 X 48644962 promoter blood 11.17 69 ENST00000377901.8 TMEM71 8 133772828 promoter blood 6.74 70 ENST00000378023.8 FAM65B 6 24877583 promoter blood 15.67 71 ENST00000378625.5 NADK 1 1711508 promoter blood 13.09 72 ENST00000379595.7 PSTPIP1 15 77287472 promoter blood 5.90 73 ENST00000380299.3 HBD 11 5255878 promoter blood 138.84 74 ENST00000380315.2 HBB 11 5250625 promoter blood 5.45 75 ENST00000381153.7 C11orf21 11 2323290 promoter blood 11.33 76 ENST00000381603.7 SIRPB1 20 1600642 promoter blood 26.01 77 ENST00000381605.8 SIRPB1 20 1600655 promoter blood 24.72 78 ENST00000382689.7 DEFA1B 8 6856717 promoter blood 118.00 79 ENST00000382692.2 DEFA1 8 6837602 promoter blood 996.76 80 ENST00000391726.7 FCAR 19 55385704 promoter blood 6.00 81 ENST00000392619.1 CD300E 17 72619877 promoter blood 24.98 82 ENST00000392621.5 CD300LB 17 72527605 promoter blood 7.72 83 ENST00000392841.1 HMBS 11 118958697 promoter blood 7.28 84 ENST00000393450.5 MYL4 17 45286714 promoter blood 22.77 85 ENST00000394430.5 RASGRP2 11 64512061 promoter blood 17.61 86 ENST00000394432.7 RASGRP2 11 64511650 promoter blood 9.91 87 ENST00000397497.8 PTK2B 8 27288416 promoter blood 5.81 88 ENST00000397797.1 HBA1 16 226703 promoter blood 25.27 89 ENST00000398421.6 NCF1 7 74188358 promoter blood 11.04 90 ENST00000398632.3 MX2 21 42774561 promoter blood 7.28 91 ENST00000399753.2 MSRB1 16 1993196 promoter blood 11.22 92 ENST00000402255.5 APOBEC3A 22 39348756 promoter blood 11.96 93 ENST00000402280.5 NLRC4 2 32489949 promoter blood 5.84 94 ENST00000404054.3 TACC3 4 1741078 promoter blood 5.17 95 ENST00000409369.1 IL18RAP 2 103036146 promoter blood 46.86 96 ENST00000410026.6 NABP1 2 192542862 promoter blood 7.35 97 ENST00000413580.5 PHOSPHO1 17 47308128 promoter blood 42.76 98 ENST00000414723.1 GCA 2 163212948 promoter blood 9.14 99 ENST00000415495.5 CEACAM3 19 42300549 promoter blood 14.84 100 ENST00000418507.6 LST1 6 31553901 promoter blood 6.17 101 ENST00000421556.5 RASGRP2 11 64511594 promoter blood 5.27 102 ENST00000421702.2 FCGR3B 1 161600948 promoter blood 18.36 103 ENST00000425417.1 ARHGAP26 5 142586765 promoter blood 5.74 104 ENST00000425515.6 VNN3 6 133055904 promoter blood 8.73 105 ENST00000426897.6 CD37 19 49838653 promoter blood 7.43 106 ENST00000427321.1 C1orf228 1 45189457 promoter blood 8.41 107 ENST00000427466.1 THEMIS2 1 28199067 promoter blood 7.94 108 ENST00000430041.6 ARHGAP9 12 57871981 promoter blood 22.12 109 ENST00000436504.2 LILRB3 19 54723224 promoter blood 69.95 110 ENST00000436693.6 TLR6 4 38858438 promoter blood 5.83 111 ENST00000441002.1 IL1R2 2 102624977 promoter blood 16.30 112 ENST00000441045.5 NAMPT 7 105925397 promoter blood 5.42 113 ENST00000441366.6 EPB42 15 43513249 promoter blood 11.69 114 ENST00000442948.3 FOLR3 11 71846989 promoter blood 9.64 115 ENST00000444257.5 PLB1 2 28827594 promoter blood 7.51 116 ENST00000445347.1 LILRB3 19 54726959 promoter blood 49.26 117 ENST00000448367.5 FES 15 91432780 promoter blood 6.30 118 ENST00000452208.1 RGL4 22 24038671 promoter blood 64.94 119 ENST00000453777.1 LILRA1 19 55105125 promoter blood 6.64 120 ENST00000455062.2 NCF1 7 74191615 promoter blood 15.11 121 ENST00000456013.5 PTPN6 12 7060434 promoter blood 7.47 122 ENST00000460045.1 IMPDH1 7 128035225 promoter blood 8.72 123 ENST00000460208.1 LILRB3 19 54721567 promoter blood 51.15 124 ENST00000460442.5 ZDHHC19 3 195925781 promoter blood 22.43 125 ENST00000460650.5 SELL 1 169673894 promoter blood 5.03 126 ENST00000462275.5 TBXAS1 7 139529072 promoter blood 6.07 127 ENST00000462927.5 CYTH4 22 37678566 promoter blood 26.95 128 ENST00000463153.1 ABHD5 3 43759160 promoter blood 5.85 129 ENST00000463516.5 MYO1G 7 45014814 promoter blood 5.23 130 ENST00000464329.1 CD53 1 111440292 promoter blood 10.28 131 ENST00000464526.1 LST1 6 31553971 promoter blood 9.98 132 ENST00000464591.1 C1orf162 1 112017190 promoter blood 7.62 133 ENST00000464994.5 IL1R2 2 102608422 promoter blood 12.24 134 ENST00000465814.5 ARAP1 11 72433133 promoter blood 10.09 135 ENST00000465984.5 SLC11A1 2 219246911 promoter blood 10.54 136 ENST00000466138.1 CSF3R 1 36933410 promoter blood 32.37 137 ENST00000466151.1 PADI2 1 17409921 promoter blood 7.13 138 ENST00000466612.5 ABTB1 3 127391857 promoter blood 6.18 139 ENST00000467001.1 PADI4 1 17675225 promoter blood 24.03 140 ENST00000467525.5 FCGR2A 1 161476123 promoter blood 8.40 141 ENST00000467786.1 FGD3 9 95737532 promoter blood 43.15 142 ENST00000467972.5 SLC12A9 7 100454416 promoter blood 6.80 143 ENST00000468221.5 SLC11A1 2 219246752 promoter blood 42.34 144 ENST00000468945.1 PADI4 1 17672529 promoter blood 17.46 145 ENST00000469273.1 LILRB3 19 54724660 promoter blood 16.30 146 ENST00000469280.1 NCF2 1 183533186 promoter blood 13.91 147 ENST00000469349.1 NBEAL2 3 47049253 promoter blood 7.54 148 ENST00000469380.1 CSF3R 1 36939431 promoter blood 5.77 149 ENST00000469449.1 SLC11A1 2 219248410 promoter blood 5.27 150 ENST00000469532.1 RAC2 22 37640318 promoter blood 9.83 151 ENST00000469799.5 SLC11A1 2 219247002 promoter blood 8.27 152 ENST00000469886.5 CYTH4 22 37678556 promoter blood 6.16 153 ENST00000470579.5 ARID5A 2 97202480 promoter blood 7.93 154 ENST00000471466.5 RAB24 5 176730706 promoter blood 6.58 155 ENST00000471836.1 PARVG 22 44577630 promoter blood 6.53 156 ENST00000472694.1 HBA1 16 226697 promoter blood 64.74 157 ENST00000473070.1 FAM65B 6 24843364 promoter blood 19.03 158 ENST00000473156.5 LILRA1 19 55105047 promoter blood 7.68 159 ENST00000473883.5 HCLS1 3 121363030 promoter blood 36.16 160 ENST00000474129.1 ABTB1 3 127395815 promoter blood 8.59 161 ENST00000475225.5 SLC11A1 2 219247025 promoter blood 37.49 162 ENST00000475472.5 FGR 1 27961645 promoter blood 49.95 163 ENST00000475683.1 TUBA4A 2 220118638 promoter blood 10.51 164 ENST00000476050.5 TRAF3IP3 1 209941940 promoter blood 5.61 165 ENST00000476408.1 CD53 1 111422859 promoter blood 10.54 166 ENST00000476492.1 LAPTM5 1 31230604 promoter blood 6.02 167 ENST00000476532.1 SASH3 X 128913955 promoter blood 9.72 168 ENST00000477720.1 LILRA5 19 54822933 promoter blood 16.70 169 ENST00000478298.5 ABTB1 3 127395379 promoter blood 6.71 170 ENST00000478902.1 ZDHHC18 1 27177620 promoter blood 12.52 171 ENST00000479534.5 PADI2 1 17401846 promoter blood 5.78 172 ENST00000479996.1 RGS19 20 62710778 promoter blood 9.02 173 ENST00000480467.5 CDK5RAP2 9 123165773 promoter blood 16.88 174 ENST00000480825.6 CSF3R 1 36941928 promoter blood 127.36 175 ENST00000481215.1 RAC2 22 37627543 promoter blood 7.04 176 ENST00000481314.5 HCLS1 3 121379748 promoter blood 13.32 177 ENST00000481517.1 STAT5B 17 40369889 promoter blood 8.48 178 ENST00000481789.1 KCNAB2 1 6156316 promoter blood 8.66 179 ENST00000482429.1 LTB 6 31550183 promoter blood 5.85 180 ENST00000482543.1 PTK2B 8 27310374 promoter blood 9.94 181 ENST00000483487.2 SLC11A1 2 219248890 promoter blood 5.23 182 ENST00000483665.6 FCGR2A 1 161475247 promoter blood 6.60 183 ENST00000483722.1 TREML2 6 41168932 promoter blood 15.58 184 ENST00000483750.5 WAS X 48542217 promoter blood 34.49 185 ENST00000484216.1 HBA2 16 222943 promoter blood 296.56 186 ENST00000484762.1 CSF3R 1 36933677 promoter blood 8.26 187 ENST00000485335.1 IL1R2 2 102639852 promoter blood 12.15 188 ENST00000485341.5 LSP1 11 1901907 promoter blood 5.48 189 ENST00000485583.1 LRCH4 7 100183752 promoter blood 5.95 190 ENST00000485743.1 HBB 11 5248302 promoter blood 128.52 191 ENST00000485991.5 CFP X 47489294 promoter blood 5.10 192 ENST00000486097.1 NCF1 7 74197786 promoter blood 12.51 193 ENST00000486327.6 DHX34 19 47870370 promoter blood 6.88 194 ENST00000486742.2 LILRA5 19 54824344 promoter blood 17.29 195 ENST00000486749.5 SLC2A3 12 8088763 promoter blood 9.53 196 ENST00000486935.2 SEMA4D 9 91996758 promoter blood 5.98 197 ENST00000487283.5 ZAP70 2 98349392 promoter blood 7.23 198 ENST00000487290.5 HCLS1 3 121379745 promoter blood 6.41 199 ENST00000487445.6 GCA 2 163200669 promoter blood 12.82 200 ENST00000487651.5 SLC12A9 7 100456358 promoter blood 6.67 201 ENST00000487761.5 GPSM3 6 32160645 promoter blood 14.37 202 ENST00000487791.1 HBA1 16 226747 promoter blood 29.54 203 ENST00000487871.1 SMAP2 1 40879649 promoter blood 36.53 204 ENST00000488945.5 GNLY 2 85912298 promoter blood 11.68 205 ENST00000488970.1 BTK X 100609209 promoter blood 7.40 206 ENST00000489175.1 KCNE1 21 35884505 promoter blood 6.75 207 ENST00000489358.5 NAMPT 7 105925396 promoter blood 30.07 208 ENST00000489551.5 CSF3R 1 36948535 promoter blood 106.01 209 ENST00000489980.5 GNLY 2 85921465 promoter blood 14.53 210 ENST00000490763.1 SLC2A3 12 8082631 promoter blood 5.93 211 ENST00000490872.1 SLC11A1 2 219254688 promoter blood 26.15 212 ENST00000491376.5 IMPDH1 7 128050036 promoter blood 6.59 213 ENST00000492413.5 SLC11A1 2 219247010 promoter blood 17.89 214 ENST00000493242.1 LILRB2 19 54784952 promoter blood 22.65 215 ENST00000493288.1 PGD 1 10472891 promoter blood 9.99 216 ENST00000493365.5 ABTB1 3 127391795 promoter blood 6.22 217 ENST00000493632.5 INPP5D 2 234078206 promoter blood 17.01 218 ENST00000493871.1 MPP1 X 154014500 promoter blood 6.09 219 ENST00000494080.5 CCDC88B 11 64109078 promoter blood 7.88 220 ENST00000494268.1 MSL3 X 11778341 promoter blood 6.22 221 ENST00000495406.1 CDK5RAP2 9 123152555 promoter blood 10.53 222 ENST00000495458.5 RAB24 5 176730682 promoter blood 11.72 223 ENST00000495988.1 APOBEC3A 22 39348746 promoter blood 40.03 224 ENST00000496379.5 FES 15 91433070 promoter blood 7.77 225 ENST00000496915.1 PREX1 20 47259276 promoter blood 5.23 226 ENST00000497441.5 RASGRP2 11 64504726 promoter blood 12.78 227 ENST00000497615.1 NADK 1 1686335 promoter blood 9.43 228 ENST00000497747.5 NADK 1 1686305 promoter blood 9.33 229 ENST00000498461.1 ALOX5 10 45938869 promoter blood 13.87 230 ENST00000498666.5 ITGB2 21 46340875 promoter blood 13.12 231 ENST00000500323.2 DOK3 5 176935878 promoter blood 10.88 232 ENST00000502380.1 DOK3 5 176937383 promoter blood 8.44 233 ENST00000504910.1 HK3 5 176318392 promoter blood 6.36 234 ENST00000505207.5 UBE2D3 4 103746937 promoter blood 7.43 235 ENST00000508794.6 NAIP 5 70316601 promoter blood 11.43 236 ENST00000509314.5 FBXL5 4 15661487 promoter blood 10.24 237 ENST00000509339.1 MXD3 5 176735063 promoter blood 30.07 238 ENST00000512426.5 CCND3 6 41908323 promoter blood 7.01 239 ENST00000512747.3 IL2RG X 70331456 promoter blood 6.21 240 ENST00000513001.5 ACSL1 4 185680030 promoter blood 17.65 241 ENST00000517804.5 DMTN 8 21914477 promoter blood 7.30 242 ENST00000517813.1 DENND3 8 142194587 promoter blood 13.47 243 ENST00000517985.5 DENND3 8 142188220 promoter blood 9.36 244 ENST00000518135.1 TNFRSF10C 8 22972020 promoter blood 5.06 245 ENST00000518249.5 DENND3 8 142151302 promoter blood 9.51 246 ENST00000518806.1 DENND3 8 142187186 promoter blood 11.76 247 ENST00000519594.5 LCP2 5 169724731 promoter blood 5.37 248 ENST00000520174.5 DMTN 8 21914416 promoter blood 16.02 249 ENST00000520322.1 LCP2 5 169678696 promoter blood 5.68 250 ENST00000520450.5 DOCK2 5 169483442 promoter blood 11.23 251 ENST00000520571.1 DENND3 8 142198997 promoter blood 8.57 252 ENST00000520887.1 FAM49B 8 130859563 promoter blood 7.15 253 ENST00000521442.1 ATP6V1B2 8 20075693 promoter blood 8.33 254 ENST00000523015.1 DENND3 8 142154013 promoter blood 7.05 255 ENST00000523022.5 CA1 8 86290342 promoter blood 40.92 256 ENST00000523066.1 DENND3 8 142183604 promoter blood 6.75 257 ENST00000523266.5 DMTN 8 21916717 promoter blood 6.93 258 ENST00000523369.1 LCP2 5 169685502 promoter blood 9.88 259 ENST00000523530.1 DENND3 8 142201373 promoter blood 7.23 260 ENST00000523615.1 STK10 5 171488634 promoter blood 12.61 261 ENST00000523829.5 TMEM71 8 133772807 promoter blood 11.05 262 ENST00000526387.5 TBC1D10C 11 67171386 promoter blood 7.10 263 ENST00000526474.1 TBC1D10C 11 67172719 promoter blood 8.87 264 ENST00000526980.5 CSF3R 1 36948500 promoter blood 184.80 265 ENST00000527031.5 JAK3 19 17958800 promoter blood 6.17 266 ENST00000527146.1 IFITM2 11 308320 promoter blood 18.56 267 ENST00000527525.5 SIPA1 11 65407337 promoter blood 5.39 268 ENST00000528086.5 CD44 11 35160718 promoter blood 8.17 269 ENST00000528780.5 IFITM1 11 313506 promoter blood 47.88 270 ENST00000530119.5 TALDO1 11 747464 promoter blood 7.74 271 ENST00000530226.1 SIPA1 11 65413282 promoter blood 6.84 272 ENST00000530587.5 PHF21A 11 45959815 promoter blood 6.25 273 ENST00000531221.5 FCGR3B 1 161600996 promoter blood 57.18 274 ENST00000531334.1 ECE1 1 21548574 promoter blood 5.78 275 ENST00000532028.1 PHF21A 11 45967420 promoter blood 5.50 276 ENST00000532362.1 CMTM2 16 66620812 promoter blood 114.27 277 ENST00000532897.5 MKNK1 1 47037972 promoter blood 6.23 278 ENST00000533815.2 BTNL8 5 180336564 promoter blood 5.72 279 ENST00000533968.1 SPI1 11 47400038 promoter blood 12.90 280 ENST00000534261.3 SIGLEC5 19 52148798 promoter blood 6.14 281 ENST00000534754.5 SORL1 11 121481961 promoter blood 9.84 282 ENST00000535615.5 CARS2 13 111318077 promoter blood 5.33 283 ENST00000535841.2 DEFA1B 8 6875811 promoter blood 962.74 284 ENST00000536885.1 ARAP1 11 72399526 promoter blood 7.74 285 ENST00000536995.5 ATG16L2 11 72532933 promoter blood 11.55 286 ENST00000538842.1 ATG16L2 11 72527790 promoter blood 6.35 287 ENST00000539134.1 RELT 11 73104289 promoter blood 6.58 288 ENST00000539932.5 SLC11A1 2 219246926 promoter blood 50.32 289 ENST00000540182.5 NLRC5 16 57074600 promoter blood 6.20 290 ENST00000540513.1 ACRBP 12 6748017 promoter blood 9.23 291 ENST00000541206.6 RNF166 16 88770025 promoter blood 11.36 292 ENST00000541623.5 ARAP1 11 72399582 promoter blood 8.01 293 ENST00000541800.6 PLBD1 12 14689059 promoter blood 6.78 294 ENST00000542481.1 ATG16L2 11 72534940 promoter blood 25.18 295 ENST00000542587.5 LPAR2 19 19739739 promoter blood 10.95 296 ENST00000543576.5 DENND1C 19 6481798 promoter blood 12.06 297 ENST00000544490.5 ATG16L2 11 72525472 promoter blood 30.13 298 ENST00000544997.5 FERMT3 11 63974150 promoter blood 7.56 299 ENST00000546200.5 ARHGAP9 12 57871634 promoter blood 66.03 300 ENST00000546704.1 ARHGAP9 12 57868923 promoter blood 19.20 301 ENST00000548139.5 ARHGAP9 12 57871842 promoter blood 15.20 302 ENST00000551000.1 ARHGAP9 12 57871650 promoter blood 8.28 303 ENST00000552953.5 ARHGAP9 12 57870424 promoter blood 24.58 304 ENST00000553070.5 NFE2 12 54694799 promoter blood 23.61 305 ENST00000553872.1 PYGL 14 51388246 promoter blood 8.64 306 ENST00000554736.5 GNG2 14 52328042 promoter blood 9.30 307 ENST00000556418.1 RIN3 14 93118846 promoter blood 12.65 308 ENST00000558177.5 ANPEP 15 90345967 promoter blood 11.96 309 ENST00000558332.3 IL16 15 81591757 promoter blood 7.66 310 ENST00000558588.5 PLCB2 15 40599894 promoter blood 12.82 311 ENST00000559341.5 MAN2A2 15 91459225 promoter blood 8.61 312 ENST00000559750.5 PSTPIP1 15 77287513 promoter blood 16.39 313 ENST00000560064.1 PSTPIP1 15 77328035 promoter blood 5.96 314 ENST00000560377.5 PSTPIP1 15 77287726 promoter blood 8.38 315 ENST00000561175.1 ADAM8 10 135086080 promoter blood 6.86 316 ENST00000562129.1 CORO1A 16 30199396 promoter blood 14.38 317 ENST00000562759.1 ST20 15 80200378 promoter blood 5.59 318 ENST00000562918.5 ITGAX 16 31366495 promoter blood 10.15 319 ENST00000563269.1 PLCG2 16 81964866 promoter blood 6.38 320 ENST00000563526.5 CYBA 16 88717396 promoter blood 7.13 321 ENST00000564072.1 SLCO3A1 15 92704805 promoter blood 8.74 322 ENST00000564572.1 CNN2 19 1036798 promoter blood 5.34 323 ENST00000564632.1 ITGAL 16 30531077 promoter blood 12.98 324 ENST00000564707.1 AHSP 16 31539298 promoter blood 6.85 325 ENST00000564768.1 CORO1A 16 30198003 promoter blood 6.01 326 ENST00000564894.1 RNF166 16 88768058 promoter blood 7.90 327 ENST00000564905.1 XPO6 16 28145246 promoter blood 12.98 328 ENST00000565076.1 SIRPB1 20 1552558 promoter blood 5.74 329 ENST00000565284.5 XPO6 16 28164239 promoter blood 14.84 330 ENST00000565497.5 CORO1A 16 30194940 promoter blood 6.42 331 ENST00000566082.1 USB1 16 58049017 promoter blood 6.82 332 ENST00000567034.5 CORO1A 16 30197253 promoter blood 11.54 333 ENST00000567038.1 XPO6 16 28113307 promoter blood 8.97 334 ENST00000567178.1 ITGAM 16 31339358 promoter blood 23.09 335 ENST00000568760.5 DEF8 16 90023661 promoter blood 7.24 336 ENST00000568982.5 CORO1A 16 30194930 promoter blood 7.54 337 ENST00000570106.6 SIGLEC5 19 52133588 promoter blood 40.53 338 ENST00000570439.1 ACAP1 17 7248650 promoter blood 5.27 339 ENST00000570473.5 TRIM25 17 54981704 promoter blood 5.32 340 ENST00000570755.1 MMP25 16 3097532 promoter blood 31.89 341 ENST00000571206.1 ARRB2 17 4618884 promoter blood 26.58 342 ENST00000571220.1 ACAP1 17 7246254 promoter blood 29.18 343 ENST00000571303.1 MLKL 16 74725367 promoter blood 5.93 344 ENST00000571791.5 ARRB2 17 4613977 promoter blood 13.94 345 ENST00000572418.1 P2RX1 17 3819746 promoter blood 9.95 346 ENST00000572666.5 CORO7 16 4411903 promoter blood 7.67 347 ENST00000572782.1 ARRB2 17 4617846 promoter blood 16.63 348 ENST00000574548.1 RNF167 17 4847675 promoter blood 6.40 349 ENST00000574888.5 ARRB2 17 4613950 promoter blood 7.24 350 ENST00000575131.5 ARRB2 17 4613956 promoter blood 11.97 351 ENST00000575441.1 MMP25 16 3106795 promoter blood 88.59 352 ENST00000576594.1 ACAP1 17 7250448 promoter blood 17.88 353 ENST00000576628.1 ACAP1 17 7239916 promoter blood 20.20 354 ENST00000576769.1 SLC43A2 17 1486992 promoter blood 5.40 355 ENST00000578574.1 SLC16A3 17 80186938 promoter blood 7.93 356 ENST00000581287.5 SLC16A3 17 80191563 promoter blood 11.97 357 ENST00000581974.1 DHRS13 17 27226541 promoter blood 5.97 358 ENST00000582174.5 FLOT2 17 27224672 promoter blood 6.46 359 ENST00000582812.5 NDEL1 17 8316449 promoter blood 9.15 360 ENST00000583093.5 SECTM1 17 80291639 promoter blood 7.78 361 ENST00000583810.5 PIK3R5 17 8785825 promoter blood 8.43 362 ENST00000584445.5 NARF 17 80438344 promoter blood 11.89 363 ENST00000585852.5 FMNL1 17 43308036 promoter blood 19.81 364 ENST00000586080.1 R3HDM4 19 901236 promoter blood 5.15 365 ENST00000587259.5 VMP1 17 57807076 promoter blood 10.58 366 ENST00000587265.1 CA4 17 58235469 promoter blood 5.45 367 ENST00000587287.1 RASGRP4 19 38902036 promoter blood 6.80 368 ENST00000587444.1 VASP 19 46029052 promoter blood 6.41 369 ENST00000587856.1 FMNL1 17 43311251 promoter blood 22.20 370 ENST00000588708.5 RASGRP4 19 38907787 promoter blood 24.68 371 ENST00000589261.5 ICAM3 19 10450295 promoter blood 6.41 372 ENST00000589900.5 ICAM3 19 10450305 promoter blood 21.24 373 ENST00000589911.1 FMNL1 17 43322691 promoter blood 7.99 374 ENST00000590227.5 DNAH17 17 76446380 promoter blood 5.85 375 ENST00000590856.1 UNC13D 17 73826742 promoter blood 6.33 376 ENST00000590974.1 LYL1 19 13213975 promoter blood 5.48 377 ENST00000591616.1 UNC13D 17 73831353 promoter blood 7.12 378 ENST00000592527.1 FMNL1 17 43310229 promoter blood 7.31 379 ENST00000594221.5 STXBP2 19 7706716 promoter blood 6.21 380 ENST00000594696.1 PRAM1 19 8556907 promoter blood 17.63 381 ENST00000594743.1 CD37 19 49840472 promoter blood 8.07 382 ENST00000595046.1 MYO1F 19 8642326 promoter blood 6.90 383 ENST00000595325.5 MYO1F 19 8642322 promoter blood 13.66 384 ENST00000595596.1 GRAMD1A 19 35503892 promoter blood 5.53 385 ENST00000595725.5 CD37 19 49838657 promoter blood 20.04 386 ENST00000596937.1 MYO1F 19 8615297 promoter blood 6.21 387 ENST00000597222.1 MYO1F 19 8604936 promoter blood 29.52 388 ENST00000597611.7 FKBP8 19 18654887 promoter blood 9.25 389 ENST00000597852.5 CD37 19 49838675 promoter blood 13.98 390 ENST00000598005.1 MYO1F 19 8606840 promoter blood 17.89 391 ENST00000598201.5 SHKBP1 19 41086073 promoter blood 12.36 392 ENST00000598529.5 MYO1F 19 8619448 promoter blood 16.08 393 ENST00000598907.5 SHKBP1 19 41084102 promoter blood 14.71 394 ENST00000598953.1 FPR2 19 52264465 promoter blood 37.43 395 ENST00000599123.1 MYO1F 19 8620661 promoter blood 7.54 396 ENST00000599180.2 FFAR2 19 35939203 promoter blood 24.79 397 ENST00000599662.1 CEACAM3 19 42312851 promoter blood 9.48 398 ENST00000599694.1 RASAL3 19 15567410 promoter blood 6.37 399 ENST00000599716.5 SHKBP1 19 41082793 promoter blood 10.66 400 ENST00000600463.1 IFI30 19 18284979 promoter blood 6.41 401 ENST00000600885.1 MYO1F 19 8592271 promoter blood 5.95 402 ENST00000601502.1 MYO1F 19 8610602 promoter blood 8.05 403 ENST00000602101.6 RASAL3 19 15575325 promoter blood 7.16 404 ENST00000602136.1 MYO1F 19 8612931 promoter blood 7.01 405 ENST00000602142.5 VAV1 19 6772737 promoter blood 8.46 406 ENST00000602166.1 EGLN2 19 41312824 promoter blood 5.19 407 ENST00000602612.5 KCNAB2 1 6086380 promoter blood 5.03 408 ENST00000605039.5 BIN2 12 51717938 promoter blood 11.02 409 ENST00000607855.5 CD177 19 43857843 promoter blood 5.94 410 ENST00000609870.5 CELF2 10 11207447 promoter blood 12.41 411 ENST00000611028.2 FOLR3 11 71846798 promoter blood 11.13 412 ENST00000612844.4 FOLR3 11 71846756 promoter blood 13.11 413 ENST00000614135.4 RASGRP4 19 38916945 promoter blood 8.18 414 ENST00000614254.1 AOAH 7 36570290 promoter blood 14.33 415 ENST00000615340.4 RASGRP4 19 38916837 promoter blood 6.88 416 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 417 ENST00000619100.4 SLC38A5 X 48325880 promoter blood 10.86 418 ENST00000620888.4 HBG2 11 5276011 promoter blood 161.14 419 ENST00000621510.1 AOAH 7 36554282 promoter blood 19.27 420 ENST00000622764.1 SAP25 7 100171443 promoter blood 5.94 421 ENST00000008938.4 PGLYRP1 19 46525993 junction blood 148.76 422 ENST00000177694.1 TBX21 17 45811311 junction blood 5.98 423 ENST00000194097.8 NAIP 5 70316486 junction blood 10.22 424 ENST00000199708.2 HBQ1 15 230580 junction blood 45.79 425 ENST00000217133.1 TUBB1 20 57594634 junction blood 6.01 426 ENST00000219596.5 MEFV 16 3306311 junction blood 19.19 427 ENST00000221804.4 CLC 19 40228578 junction blood 19.65 428 ENST00000221954.6 CEACAM4 19 42133268 junction blood 32.81 429 ENST00000225275.3 MPO 17 56357966 junction blood 7.23 430 ENST00000233997.3 AZU1 19 827904 junction blood 14.03 431 ENST00000234347.9 PRTN3 19 841069 junction blood 13.78 432 ENST00000236826.7 MMP8 11 102595485 junction blood 20.68 433 ENST00000245620.13 LILRB3 19 54726815 junction blood 22.83 434 ENST00000258104.7 DYSF 2 71681216 junction blood 6.76 435 ENST00000262407.5 ITGA2B 17 42466654 junction blood 12.34 436 ENST00000262651.3 HCK 20 30640289 junction blood 8.74 437 ENST00000262865.8 BPI 20 36932755 junction blood 18.06 438 ENST00000263621.1 ELANE 19 852395 junction blood 21.67 439 ENST00000264260.6 IL18RAP 2 103035400 junction blood 42.11 440 ENST00000264834.4 KLF1 19 12997868 junction blood 8.95 441 ENST00000267396.8 REM2 14 23352599 junction blood 6.91 442 ENST00000287497.12 ITGAM 16 31271413 junction blood 6.52 443 ENST00000294800.7 FCGR3B 1 161600845 junction blood 13.85 444 ENST00000295619.3 PROK2 3 71834108 junction blood 12.98 445 ENST00000295683.2 CXCR1 2 219031631 junction blood 355.57 446 ENST00000296028.3 PPBP 4 74853673 junction blood 50.15 447 ENST00000296435.2 CAMP 3 48265202 junction blood 27.17 448 ENST00000297435.2 DEFA4 8 6795748 junction blood 34.98 449 ENST00000299663.7 CLEC4E 12 8693357 junction blood 29.27 450 ENST00000299665.2 CLEC4D 12 8666356 junction blood 10.47 451 ENST00000302312.8 AHSP 16 31539283 junction blood 85.51 452 ENST00000304076.6 VAV1 19 6773022 junction blood 7.61 453 ENST00000304361.8 CLEC12A 12 10124286 junction blood 10.23 454 ENST00000307395.4 GP9 3 128779693 junction blood 9.72 455 ENST00000307564.8 AKNA 9 117156637 junction blood 11.95 456 ENST00000310544.8 PHOSPHO1 17 47307830 junction blood 30.92 457 ENST00000312156.8 NFE2 12 54689328 junction blood 11.15 458 ENST00000314412.6 FUT7 9 139926431 junction blood 16.90 459 ENST00000314446.9 LILRB2 19 54784816 junction blood 7.87 460 ENST00000318507.6 CXCR2 2 218991076 junction blood 157.27 461 ENST00000324134.10 NLRP12 19 54327140 junction blood 9.17 462 ENST00000326965.6 TAGAP 6 159465911 junction blood 5.94 463 ENST00000327857.6 DEFA3 8 6875744 junction blood 355.10 464 ENST00000329800.7 TMCC2 1 205225544 junction blood 10.64 465 ENST00000330597.3 HBG1 11 5270943 junction blood 5.07 466 ENST00000330807.9 ALAS2 X 55057375 junction blood 142.66 467 ENST00000331941.6 CSF3R 1 36945034 junction blood 16.12 468 ENST00000336906.4 HBG2 11 5275867 junction blood 104.85 469 ENST00000338372.6 VSTM1 19 54566998 junction blood 10.71 470 ENST00000340023.6 FPR2 19 52264483 junction blood 34.71 471 ENST00000342063.4 C19orf35 19 2282086 junction blood 8.64 472 ENST00000342571.7 MKNK1 1 47051546 junction blood 14.42 473 ENST00000344138.8 GRAP2 22 40297334 junction blood 5.60 474 ENST00000348343.10 BMX X 15519063 junction blood 6.99 475 ENST00000355524.7 FCAR 19 55385779 junction blood 53.04 476 ENST00000356815.3 HBM 16 216088 junction blood 163.82 477 ENST00000357396.7 CEACAM3 19 42300673 junction blood 16.26 478 ENST00000367053.5 CR1 1 207669733 junction blood 10.47 479 ENST00000367964.6 FCGR3B 1 161601676 junction blood 465.71 480 ENST00000368034.8 CD244 1 160832407 junction blood 6.27 481 ENST00000373103.5 CSF3R 1 36948412 junction blood 61.20 482 ENST00000375448.4 PADI4 1 17634809 junction blood 95.04 483 ENST00000375809.7 C6orf25 6 31691221 junction blood 5.36 484 ENST00000376092.7 LST1 6 31555095 junction blood 5.01 485 ENST00000376670.7 GATA1 X 48645053 junction blood 11.17 486 ENST00000377901.8 TMEM71 8 133772722 junction blood 6.74 487 ENST00000378023.8 FAM65B 6 24877179 junction blood 15.67 488 ENST00000378625.5 NADK 1 1711344 junction blood 13.09 489 ENST00000379595.7 PSTPIP1 15 77287950 junction blood 5.90 490 ENST00000380299.3 HBD 11 5255572 junction blood 138.84 491 ENST00000380315.2 HBB 11 5250482 junction blood 5.45 492 ENST00000381153.7 C11orf21 11 2322986 junction blood 11.33 493 ENST00000381603.7 SIRPB1 20 1600515 junction blood 26.01 494 ENST00000382689.7 DEFA1B 8 6856645 junction blood 118.00 495 ENST00000382692.2 DEFA1 8 6837535 junction blood 996.76 496 ENST00000392619.1 CD300E 17 72619721 junction blood 24.98 497 ENST00000392621.5 CD300LB 17 72527450 junction blood 7.72 498 ENST00000392841.1 HMBS 11 118958788 junction blood 7.28 499 ENST00000393450.5 MYL4 17 45286923 junction blood 22.77 500 ENST00000394430.5 RASGRP2 11 64510266 junction blood 17.61 501 ENST00000394432.7 RASGRP2 11 64511475 junction blood 9.91 502 ENST00000397497.8 PTK2B 8 27288989 junction blood 5.81 503 ENST00000397797.1 HBA1 16 226761 junction blood 25.27 504 ENST00000398421.6 NCF1 7 74188450 junction blood 11.04 505 ENST00000398632.3 MX2 21 42775563 junction blood 7.28 506 ENST00000399753.2 MSRB1 16 1993103 junction blood 11.22 507 ENST00000402255.5 APOBEC3A 22 39348855 junction blood 11.96 508 ENST00000402280.5 NLRC4 2 32489807 junction blood 5.84 509 ENST00000404054.3 TACC3 4 1743848 junction blood 5.17 510 ENST00000409369.1 IL18RAP 2 103036257 junction blood 46.86 511 ENST00000410026.6 NABP1 2 192542967 junction blood 7.35 512 ENST00000414723.1 GCA 2 163212991 junction blood 9.14 513 ENST00000418507.6 LST1 6 31554092 junction blood 6.17 514 ENST00000425417.1 ARHGAP26 5 142586873 junction blood 5.74 515 ENST00000425515.6 VNN3 6 133055619 junction blood 8.73 516 ENST00000426897.6 CD37 19 49838832 junction blood 7.43 517 ENST00000427321.1 C1orf228 1 45189578 junction blood 8.41 518 ENST00000427466.1 THEMIS2 1 28199176 junction blood 7.94 519 ENST00000430041.6 ARHGAP9 12 57871568 junction blood 22.12 520 ENST00000436504.2 LILRB3 19 54722998 junction blood 69.95 521 ENST00000436693.6 TLR6 4 38858382 junction blood 5.83 522 ENST00000441002.1 IL1R2 2 102625104 junction blood 16.30 523 ENST00000441045.5 NAMPT 7 105925274 junction blood 5.42 524 ENST00000441366.6 EPB42 15 43513014 junction blood 11.69 525 ENST00000442948.3 FOLR3 11 71847166 junction blood 9.64 526 ENST00000444257.5 PLB1 2 28827626 junction blood 7.51 527 ENST00000448367.5 FES 15 91432866 junction blood 6.30 528 ENST00000452208.1 RGL4 22 24038875 junction blood 64.94 529 ENST00000453777.1 LILRA1 19 55105246 junction blood 6.64 530 ENST00000455062.2 NCF1 7 74191693 junction blood 15.11 531 ENST00000456013.5 PTPN6 12 7060683 junction blood 7.47 532 ENST00000460045.1 IMPDH1 7 128035185 junction blood 8.72 533 ENST00000460208.1 LILRB3 19 54721188 junction blood 51.15 534 ENST00000460442.5 ZDHHC19 3 195925660 junction blood 22.43 535 ENST00000460650.5 SELL 1 169673709 junction blood 5.03 536 ENST00000462275.5 TBXAS1 7 139529278 junction blood 6.07 537 ENST00000462927.5 CYTH4 22 37678629 junction blood 26.95 538 ENST00000463153.1 ABHD5 3 43759349 junction blood 5.85 539 ENST00000463516.5 MYO1G 7 45014773 junction blood 5.23 540 ENST00000464329.1 CD53 1 111440514 junction blood 10.28 541 ENST00000464591.1 C1orf162 1 112018687 junction blood 7.62 542 ENST00000464994.5 IL1R2 2 102608495 junction blood 12.24 543 ENST00000465814.5 ARAP1 11 72432895 junction blood 10.09 544 ENST00000465984.5 SLC11A1 2 219247098 junction blood 10.54 545 ENST00000466138.1 CSF3R 1 36933159 junction blood 32.37 546 ENST00000466151.1 PADI2 1 17409731 junction blood 7.13 547 ENST00000466612.5 ABTB1 3 127392451 junction blood 6.18 548 ENST00000467001.1 PADI4 1 17675280 junction blood 24.03 549 ENST00000467525.5 FCGR2A 1 161476381 junction blood 8.40 550 ENST00000467786.1 FGD3 9 95737687 junction blood 43.15 551 ENST00000467972.5 SLC12A9 7 100456564 junction blood 6.80 552 ENST00000468945.1 PADI4 1 17672634 junction blood 17.46 553 ENST00000469273.1 LILRB3 19 54724398 junction blood 16.30 554 ENST00000469280.1 NCF2 1 183532569 junction blood 13.91 555 ENST00000469349.1 NBEAL2 3 47049676 junction blood 7.54 556 ENST00000469380.1 CSF3R 1 36939365 junction blood 5.77 557 ENST00000469449.1 SLC11A1 2 219249088 junction blood 5.27 558 ENST00000469532.1 RAC2 22 37640154 junction blood 9.83 559 ENST00000470579.5 ARID5A 2 97202567 junction blood 7.93 560 ENST00000471466.5 RAB24 5 176730010 junction blood 6.58 561 ENST00000471836.1 PARVG 22 44577797 junction blood 6.53 562 ENST00000472694.1 HBA1 16 227132 junction blood 64.74 563 ENST00000473070.1 FAM65B 6 24843090 junction blood 19.03 564 ENST00000473883.5 HCLS1 3 121361774 junction blood 36.16 565 ENST00000474129.1 ABTB1 3 127395926 junction blood 8.59 566 ENST00000475472.5 FGR 1 27961576 junction blood 49.95 567 ENST00000475683.1 TUBA4A 2 220118578 junction blood 10.51 568 ENST00000476050.5 TRAF3IP3 1 209942005 junction blood 5.61 569 ENST00000476408.1 CD53 1 111422954 junction blood 10.54 570 ENST00000476492.1 LAPTM5 1 31230506 junction blood 6.02 571 ENST00000476532.1 SASH3 X 128914130 junction blood 9.72 572 ENST00000477720.1 LILRA5 19 54822684 junction blood 16.70 573 ENST00000478298.5 ABTB1 3 127395424 junction blood 6.71 574 ENST00000478902.1 ZDHHC18 1 27177722 junction blood 12.52 575 ENST00000479534.5 PADI2 1 17401351 junction blood 5.78 576 ENST00000479996.1 RGS19 20 62710647 junction blood 9.02 577 ENST00000480467.5 CDK5RAP2 9 123165521 junction blood 16.88 578 ENST00000480825.6 CSF3R 1 36940978 junction blood 127.36 579 ENST00000481215.1 RAC2 22 37627271 junction blood 7.04 580 ENST00000481314.5 HCLS1 3 121379667 junction blood 13.32 581 ENST00000481517.1 STAT5B 17 40369395 junction blood 8.48 582 ENST00000481789.1 KCNAB2 1 6156816 junction blood 8.66 583 ENST00000482429.1 LTB 6 31549336 junction blood 5.85 584 ENST00000482543.1 PTK2B 8 27310677 junction blood 9.94 585 ENST00000483665.6 FCGR2A 1 161475342 junction blood 6.60 586 ENST00000483722.1 TREML2 6 41168692 junction blood 15.58 587 ENST00000483750.5 WAS X 48542374 junction blood 34.49 588 ENST00000484216.1 HBA2 16 223006 junction blood 296.56 589 ENST00000484762.1 CSF3R 1 36933423 junction blood 8.26 590 ENST00000485335.1 IL1R2 2 102640083 junction blood 12.15 591 ENST00000485341.5 LSP1 11 1902593 junction blood 5.48 592 ENST00000485583.1 LRCH4 7 100183504 junction blood 5.95 593 ENST00000485743.1 HBB 11 5248160 junction blood 128.52 594 ENST00000485991.5 CFP X 47489168 junction blood 5.10 595 ENST00000486097.1 NCF1 7 74197975 junction blood 12.51 596 ENST00000486327.6 DHX34 19 47870412 junction blood 6.88 597 ENST00000486742.2 LILRA5 19 54824287 junction blood 17.29 598 ENST00000486749.5 SLC2A3 12 8088616 junction blood 9.53 599 ENST00000486935.2 SEMA4D 9 91996089 junction blood 5.98 600 ENST00000487283.5 ZAP70 2 98349484 junction blood 7.23 601 ENST00000487445.6 GCA 2 163200785 junction blood 12.82 602 ENST00000487651.5 SLC12A9 7 100459206 junction blood 6.67 603 ENST00000487761.5 GPSM3 6 32160249 junction blood 14.37 604 ENST00000487791.1 HBA1 16 226810 junction blood 29.54 605 ENST00000487871.1 SMAP2 1 40879912 junction blood 36.53 606 ENST00000488945.5 GNLY 2 85912344 junction blood 11.68 607 ENST00000488970.1 BTK X 100608858 junction blood 7.40 608 ENST00000489175.1 KCNE1 21 35884325 junction blood 6.75 609 ENST00000489980.5 GNLY 2 85922546 junction blood 14.53 610 ENST00000490763.1 SLC2A3 12 8082280 junction blood 5.93 611 ENST00000490872.1 SLC11A1 2 219254751 junction blood 26.15 612 ENST00000491376.5 IMPDH1 7 128049810 junction blood 6.59 613 ENST00000493288.1 PGD 1 10473308 junction blood 9.99 614 ENST00000493365.5 ABTB1 3 127391924 junction blood 6.22 615 ENST00000493632.5 INPP5D 2 234078810 junction blood 17.01 616 ENST00000493871.1 MPP1 X 154014479 junction blood 6.09 617 ENST00000494080.5 CCDC88B 11 64109214 junction blood 7.88 618 ENST00000494268.1 MSL3 X 11778428 junction blood 6.22 619 ENST00000495406.1 CDK5RAP2 9 123152019 junction blood 10.53 620 ENST00000496379.5 FES 15 91433192 junction blood 7.77 621 ENST00000496915.1 PREX1 20 47258945 junction blood 5.23 622 ENST00000497441.5 RASGRP2 11 64504225 junction blood 12.78 623 ENST00000497615.1 NADK 1 1685983 junction blood 9.43 624 ENST00000498461.1 ALOX5 10 45938985 junction blood 13.87 625 ENST00000498666.5 ITGB2 21 46340736 junction blood 13.12 626 ENST00000500323.2 DOK3 5 176935238 junction blood 10.88 627 ENST00000502380.1 DOK3 5 176937261 junction blood 8.44 628 ENST00000504910.1 HK3 5 176318389 junction blood 6.36 629 ENST00000505207.5 UBE2D3 4 103746879 junction blood 7.43 630 ENST00000509314.5 FBXL5 4 15661350 junction blood 10.24 631 ENST00000509339.1 MXD3 5 176734782 junction blood 30.07 632 ENST00000512426.5 CCND3 6 41908108 junction blood 7.01 633 ENST00000512747.3 IL2RG X 70331275 junction blood 6.21 634 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 635 ENST00000517804.5 DMTN 8 21914647 junction blood 7.30 636 ENST00000517813.1 DENND3 8 142195377 junction blood 13.47 637 ENST00000517985.5 DENND3 8 142188295 junction blood 9.36 638 ENST00000518135.1 TNFRSF10C 8 22972283 junction blood 5.06 639 ENST00000518249.5 DENND3 8 142151423 junction blood 9.51 640 ENST00000519594.5 LCP2 5 169724538 junction blood 5.37 641 ENST00000520322.1 LCP2 5 169677734 junction blood 5.68 642 ENST00000520450.5 DOCK2 5 169484670 junction blood 11.23 643 ENST00000520571.1 DENND3 8 142199245 junction blood 8.57 644 ENST00000520887.1 FAM49B 8 130859050 junction blood 7.15 645 ENST00000521442.1 ATP6V1B2 8 20075793 junction blood 8.33 646 ENST00000523015.1 DENND3 8 142154358 junction blood 7.05 647 ENST00000523022.5 CA1 8 86290275 junction blood 40.92 648 ENST00000523066.1 DENND3 8 142183840 junction blood 6.75 649 ENST00000523266.5 DMTN 8 21917007 junction blood 6.93 650 ENST00000523369.1 LCP2 5 169685041 junction blood 9.88 651 ENST00000523530.1 DENND3 8 142202548 junction blood 7.23 652 ENST00000523615.1 STK10 5 171488143 junction blood 12.61 653 ENST00000526387.5 TBC1D10C 11 67171411 junction blood 7.10 654 ENST00000526474.1 TBC1D10C 11 67172977 junction blood 8.87 655 ENST00000527031.5 JAK3 19 17958755 junction blood 6.17 656 ENST00000527146.1 IFITM2 11 308438 junction blood 18.56 657 ENST00000527525.5 SIPA1 11 65407492 junction blood 5.39 658 ENST00000528086.5 CD44 11 35160917 junction blood 8.17 659 ENST00000528780.5 IFITM1 11 313691 junction blood 47.88 660 ENST00000530119.5 TALDO1 11 747578 junction blood 7.74 661 ENST00000530226.1 SIPA1 11 65413428 junction blood 6.84 662 ENST00000530587.5 PHF21A 11 45959708 junction blood 6.25 663 ENST00000531334.1 ECE1 1 21548240 junction blood 5.78 664 ENST00000532028.1 PHF21A 11 45967391 junction blood 5.50 665 ENST00000532362.1 CMTM2 16 66621001 junction blood 114.27 666 ENST00000532897.5 MKNK1 1 47037735 junction blood 6.23 667 ENST00000533815.2 BTNL8 5 180336697 junction blood 5.72 668 ENST00000533968.1 SPI1 11 47399860 junction blood 12.90 669 ENST00000534261.3 SIGLEC5 19 52148730 junction blood 6.14 670 ENST00000534754.5 SORL1 11 121483541 junction blood 9.84 671 ENST00000535615.5 CARS2 13 111317875 junction blood 5.33 672 ENST00000536885.1 ARAP1 11 72399500 junction blood 7.74 673 ENST00000536995.5 ATG16L2 11 72533340 junction blood 11.55 674 ENST00000538842.1 ATG16L2 11 72527872 junction blood 6.35 675 ENST00000539134.1 RELT 11 73104962 junction blood 6.58 676 ENST00000540182.5 NLRC5 16 57074630 junction blood 6.20 677 ENST00000540513.1 ACRBP 12 6747841 junction blood 9.23 678 ENST00000541206.6 RNF166 16 88769198 junction blood 11.36 679 ENST00000541800.6 PLBD1 12 14688593 junction blood 6.78 680 ENST00000542481.1 ATG16L2 11 72535167 junction blood 25.18 681 ENST00000542587.5 LPAR2 19 19739237 junction blood 10.95 682 ENST00000543576.5 DENND1C 19 6481690 junction blood 12.06 683 ENST00000544490.5 ATG16L2 11 72525608 junction blood 30.13 684 ENST00000544997.5 FERMT3 11 63974286 junction blood 7.56 685 ENST00000546704.1 ARHGAP9 12 57868658 junction blood 19.20 686 ENST00000548139.5 ARHGAP9 12 57871784 junction blood 15.20 687 ENST00000552953.5 ARHGAP9 12 57870373 junction blood 24.58 688 ENST00000553070.5 NFE2 12 54694585 junction blood 23.61 689 ENST00000553872.1 PYGL 14 51387674 junction blood 8.64 690 ENST00000554736.5 GNG2 14 52328108 junction blood 9.30 691 ENST00000556418.1 RIN3 14 93119420 junction blood 12.65 692 ENST00000558177.5 ANPEP 15 90345638 junction blood 11.96 693 ENST00000558332.3 IL16 15 81592816 junction blood 7.66 694 ENST00000558588.5 PLCB2 15 40599790 junction blood 12.82 695 ENST00000559341.5 MAN2A2 15 91459486 junction blood 8.61 696 ENST00000560064.1 PSTPIP1 15 77328276 junction blood 5.96 697 ENST00000561175.1 ADAM8 10 135085920 junction blood 6.86 698 ENST00000562129.1 CORO1A 16 30199570 junction blood 14.38 699 ENST00000562759.1 ST20 15 80199971 junction blood 5.59 700 ENST00000562918.5 ITGAX 16 31366612 junction blood 10.15 701 ENST00000563269.1 PLCG2 16 81965259 junction blood 6.38 702 ENST00000563526.5 CYBA 16 88717364 junction blood 7.13 703 ENST00000564072.1 SLCO3A1 15 92706776 junction blood 8.74 704 ENST00000564572.1 CNN2 19 1039063 junction blood 5.34 705 ENST00000564632.1 ITGAL 16 30531288 junction blood 12.98 706 ENST00000564707.1 AHSP 16 31539335 junction blood 6.85 707 ENST00000564768.1 CORO1A 16 30198544 junction blood 6.01 708 ENST00000564894.1 RNF166 16 88767670 junction blood 7.90 709 ENST00000564905.1 XPO6 16 28145162 junction blood 12.98 710 ENST00000565076.1 SIRPB1 20 1552366 junction blood 5.74 711 ENST00000565284.5 XPO6 16 28163980 junction blood 14.84 712 ENST00000565497.5 CORO1A 16 30195046 junction blood 6.42 713 ENST00000566082.1 USB1 16 58051343 junction blood 6.82 714 ENST00000567034.5 CORO1A 16 30198041 junction blood 11.54 715 ENST00000567038.1 XPO6 16 28113168 junction blood 8.97 716 ENST00000567178.1 ITGAM 16 31339551 junction blood 23.09 717 ENST00000568760.5 DEF8 16 90024068 junction blood 7.24 718 ENST00000570106.6 SIGLEC5 19 52133552 junction blood 40.53 719 ENST00000570439.1 ACAP1 17 7253547 junction blood 5.27 720 ENST00000570473.5 TRIM25 17 54981616 junction blood 5.32 721 ENST00000570755.1 MMP25 16 3097548 junction blood 31.89 722 ENST00000571206.1 ARRB2 17 4619328 junction blood 26.58 723 ENST00000571220.1 ACAP1 17 7246881 junction blood 29.18 724 ENST00000571303.1 MLKL 16 74725175 junction blood 5.93 725 ENST00000571791.5 ARRB2 17 4614039 junction blood 13.94 726 ENST00000572418.1 P2RX1 17 3819383 junction blood 9.95 727 ENST00000572666.5 CORO7 16 4411362 junction blood 7.67 728 ENST00000572782.1 ARRB2 17 4618338 junction blood 16.63 729 ENST00000574548.1 RNF167 17 4847933 junction blood 6.40 730 ENST00000575441.1 MMP25 16 3107210 junction blood 88.59 731 ENST00000576594.1 ACAP1 17 7250561 junction blood 17.88 732 ENST00000576628.1 ACAP1 17 7240106 junction blood 20.20 733 ENST00000576769.1 SLC43A2 17 1486498 junction blood 5.40 734 ENST00000578574.1 SLC16A3 17 80186982 junction blood 7.93 735 ENST00000581287.5 SLC16A3 17 80194107 junction blood 11.97 736 ENST00000581974.1 DHRS13 17 27226145 junction blood 5.97 737 ENST00000582174.5 FLOT2 17 27224544 junction blood 6.46 738 ENST00000582812.5 NDEL1 17 8316587 junction blood 9.15 739 ENST00000583093.5 SECTM1 17 80291576 junction blood 7.78 740 ENST00000583810.5 PIK3R5 17 8785105 junction blood 8.43 741 ENST00000584445.5 NARF 17 80439087 junction blood 11.89 742 ENST00000585852.5 FMNL1 17 43308054 junction blood 19.81 743 ENST00000586080.1 R3HDM4 19 900829 junction blood 5.15 744 ENST00000587259.5 VMP1 17 57807378 junction blood 10.58 745 ENST00000587265.1 CA4 17 58235488 junction blood 5.45 746 ENST00000587287.1 RASGRP4 19 38901755 junction blood 6.80 747 ENST00000587444.1 VASP 19 46029261 junction blood 6.41 748 ENST00000587856.1 FMNL1 17 43311567 junction blood 22.20 749 ENST00000588708.5 RASGRP4 19 38907692 junction blood 24.68 750 ENST00000589261.5 ICAM3 19 10450215 junction blood 6.41 751 ENST00000589911.1 FMNL1 17 43322783 junction blood 7.99 752 ENST00000590227.5 DNAH17 17 76445496 junction blood 5.85 753 ENST00000590856.1 UNC13D 17 73826659 junction blood 6.33 754 ENST00000590974.1 LYL1 19 13213345 junction blood 5.48 755 ENST00000591616.1 UNC13D 17 73831001 junction blood 7.12 756 ENST00000592527.1 FMNL1 17 43310664 junction blood 7.31 757 ENST00000594221.5 STXBP2 19 7706739 junction blood 6.21 758 ENST00000594696.1 PRAM1 19 8555984 junction blood 17.63 759 ENST00000594743.1 CD37 19 49840478 junction blood 8.07 760 ENST00000595046.1 MYO1F 19 8641326 junction blood 6.90 761 ENST00000595325.5 MYO1F 19 8642191 junction blood 13.66 762 ENST00000595596.1 GRAMD1A 19 35504595 junction blood 5.53 763 ENST00000595725.5 CD37 19 49838866 junction blood 20.04 764 ENST00000596937.1 MYO1F 19 8615044 junction blood 6.21 765 ENST00000597222.1 MYO1F 19 8604831 junction blood 29.52 766 ENST00000597611.7 FKBP8 19 18654719 junction blood 9.25 767 ENST00000598005.1 MYO1F 19 8606797 junction blood 17.89 768 ENST00000598201.5 SHKBP1 19 41086391 junction blood 12.36 769 ENST00000598529.5 MYO1F 19 8619361 junction blood 16.08 770 ENST00000598907.5 SHKBP1 19 41084448 junction blood 14.71 771 ENST00000599123.1 MYO1F 19 8620543 junction blood 7.54 772 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 773 ENST00000599662.1 CEACAM3 19 42312968 junction blood 9.48 774 ENST00000599694.1 RASAL3 19 15567313 junction blood 6.37 775 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 776 ENST00000600463.1 IFI30 19 18286032 junction blood 6.41 777 ENST00000600885.1 MYO1F 19 8592222 junction blood 5.95 778 ENST00000601502.1 MYO1F 19 8610534 junction blood 8.05 779 ENST00000602101.6 RASAL3 19 15575316 junction blood 7.16 780 ENST00000602136.1 MYO1F 19 8612920 junction blood 7.01 781 ENST00000602166.1 EGLN2 19 41313179 junction blood 5.19 782 ENST00000602612.5 KCNAB2 1 6086505 junction blood 5.03 783 ENST00000605039.5 BIN2 12 51717806 junction blood 11.02 784 ENST00000607855.5 CD177 19 43857918 junction blood 5.94 785 ENST00000609870.5 CELF2 10 11207645 junction blood 12.41 786 ENST00000611028.2 FOLR3 11 71846814 junction blood 11.13 787 ENST00000614135.4 RASGRP4 19 38916709 junction blood 8.18 788 ENST00000614254.1 AOAH 7 36570024 junction blood 14.33 789 ENST00000616356.4 FCN1 9 137809615 junction blood 16.99 790 ENST00000619100.4 SLC38A5 X 48325349 junction blood 10.86 791 ENST00000621510.1 AOAH 7 36554078 junction blood 19.27 792 ENST00000622764.1 SAP25 7 100171220 junction blood 5.94 Columns ID: feature index Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood. Their FPKM values in tumors of 20 cancer types are all <1.

TABLE S11 Observed ctDNA fractions in the LOD analysis for the CRC + BRCA model. Expected ctDNA Observed ctDNA Sample Group fractions fraction 1279_221015-0.005 positive 0.0050 0.0194 1279_221015-0.010 positive 0.0100 0.0245 1279_221015-0.015 positive 0.0150 0.0364 1279_221015-0.020 positive 0.0200 0.0361 1279_221015-0.025 positive 0.0250 0.0482 1279_221015-0.030 positive 0.0300 0.0515 1279_221015-0.035 positive 0.0350 0.0597 1279_221015-0.040 positive 0.0400 0.0721 1279_221015-0.045 positive 0.0450 0.0631 1279_221015-0.050 positive 0.0500 0.0652 1279_221015-0.075 positive 0.0750 0.0837 1279_221015-0.100 positive 0.1000 0.1084 1279_221015-0.125 positive 0.1250 0.1332 1279_221015-0.150 positive 0.1500 0.1566 1279_221015-0.175 positive 0.1750 0.1561 1279_221015-0.200 positive 0.2000 0.1770 1279_221015-0.225 positive 0.2250 0.1910 1279_221015-0.250 positive 0.2500 0.2421 1279_221015-0.275 positive 0.2750 0.2313 1279_221015-0.300 positive 0.3000 0.2821 1279_221015-0.325 positive 0.3250 0.3011 1279_221015-0.350 positive 0.3500 0.3237 1279_221015-0.375 positive 0.3750 0.3630 1279_221015-0.400 positive 0.4000 0.3893 1279_221015-0.425 positive 0.4250 0.4190 1279_221015-0.450 positive 0.4500 0.4658 1279_221015-0.475 positive 0.4750 0.4764 1279_221015-0.500 positive 0.5000 0.4699 1279_241116-0.005 positive 0.0050 0.0252 1279_241116-0.010 positive 0.0100 0.0143 1279_241116-0.015 positive 0.0150 0.0230 1279_241116-0.020 positive 0.0200 0.0242 1279_241116-0.025 positive 0.0250 0.0385 1279_241116-0.030 positive 0.0300 0.0310 1279_241116-0.035 positive 0.0350 0.0426 1279_241116-0.040 positive 0.0400 0.0407 1279_241116-0.045 positive 0.0450 0.0418 1279_241116-0.050 positive 0.0500 0.0457 1279_241116-0.075 positive 0.0750 0.0761 1279_241116-0.100 positive 0.1000 0.1275 1279_241116-0.125 positive 0.1250 0.1369 1279_241116-0.150 positive 0.1500 0.1199 1279_241116-0.175 positive 0.1750 0.1242 1279_241116-0.200 positive 0.2000 0.1394 1279_241116-0.225 positive 0.2250 0.1577 1279_241116-0.250 positive 0.2500 0.1860 1279_241116-0.275 positive 0.2750 0.2301 1279_241116-0.300 positive 0.3000 0.2666 1279_241116-0.325 positive 0.3250 0.3036 1279_241116-0.350 positive 0.3500 0.2946 1279_241116-0.375 positive 0.3750 0.3256 1279_241116-0.400 positive 0.4000 0.3788 1279_241116-0.425 positive 0.4250 0.4033 1279_241116-0.450 positive 0.4500 0.4591 1279_241116-0.475 positive 0.4750 0.4359 1279_241116-0.490 positive 0.4900 0.4611 512_051015-0.005 positive 0.0050 0.0273 512_051015-0.010 positive 0.0100 0.0221 512_051015-0.015 positive 0.0150 0.0301 512_051015-0.020 positive 0.0200 0.0252 512_051015-0.025 positive 0.0250 0.0283 512_051015-0.030 positive 0.0300 0.0233 512_051015-0.035 positive 0.0350 0.0485 512_051015-0.040 positive 0.0400 0.0712 512_051015-0.045 positive 0.0450 0.0793 512_051015-0.050 positive 0.0500 0.0947 512_051015-0.075 positive 0.0750 0.1269 512_051015-0.100 positive 0.1000 0.1528 512_051015-0.125 positive 0.1250 0.1788 512_051015-0.150 positive 0.1500 0.2018 512_051015-0.175 positive 0.1750 0.2097 512_051015-0.200 positive 0.2000 0.2359 512_051015-0.225 positive 0.2250 0.2709 512_051015-0.250 positive 0.2500 0.2759 512_051015-0.275 positive 0.2750 0.2731 512_051015-0.300 positive 0.3000 0.2930 512_051015-0.325 positive 0.3250 0.3230 512_051015-0.350 positive 0.3500 0.3364 512_051015-0.375 positive 0.3750 0.3723 512_051015-0.400 positive 0.4000 0.4192 512_051015-0.425 positive 0.4250 0.4303 512_051015-0.450 positive 0.4500 0.4825 512_051015-0.475 positive 0.4750 0.4897 512_051015-0.500 positive 0.5000 0.5015 512_051015-0.525 positive 0.5250 0.5312 512_051015-0.550 positive 0.5500 0.5683 512_051015-0.575 positive 0.5750 0.5989 512_051015-0.600 positive 0.6000 0.6028 512_051015-0.614 positive 0.6140 0.5969 512_130114-0.005 positive 0.0050 0.0308 512_130114-0.010 positive 0.0100 0.0283 512_130114-0.015 positive 0.0150 0.0118 512_130114-0.020 positive 0.0200 0.0000 512_130114-0.025 positive 0.0250 0.0167 512_130114-0.030 positive 0.0300 0.0283 512_130114-0.035 positive 0.0350 0.0565 512_130114-0.040 positive 0.0400 0.0616 512_130114-0.045 positive 0.0450 0.0454 512_130114-0.050 positive 0.0500 0.0398 512_130114-0.075 positive 0.0750 0.0774 512_130114-0.100 positive 0.1000 0.0893 512_130114-0.125 positive 0.1250 0.1541 512_130114-0.150 positive 0.1500 0.1891 512_130114-0.175 positive 0.1750 0.1988 512_130114-0.200 positive 0.2000 0.2222 512_130114-0.225 positive 0.2250 0.2824 512_130114-0.250 positive 0.2500 0.3523 512_130114-0.275 positive 0.2750 0.3871 512_130114-0.300 positive 0.3000 0.4119 512_130114-0.325 positive 0.3250 0.4908 512_130114-0.350 positive 0.3500 0.5099 512_130114-0.375 positive 0.3750 0.5502 512_130114-0.394 positive 0.3940 0.5966 D19-0.005 positive 0.0050 0.0226 D19-0.010 positive 0.0100 0.0232 D19-0.015 positive 0.0150 0.0205 D19-0.020 positive 0.0200 0.0316 D19-0.025 positive 0.0250 0.0438 D19-0.030 positive 0.0300 0.0458 D19-0.035 positive 0.0350 0.0525 D19-0.040 positive 0.0400 0.0458 D19-0.045 positive 0.0450 0.0405 D19-0.050 positive 0.0500 0.0400 D19-0.075 positive 0.0750 0.0745 D19-0.100 positive 0.1000 0.1132 D19-0.125 positive 0.1250 0.1275 D19-0.150 positive 0.1500 0.1471 D19-0.175 positive 0.1750 0.1751 D19-0.200 positive 0.2000 0.1870 D19-0.225 positive 0.2250 0.1984 D19-0.250 positive 0.2500 0.2162 D19-0.275 positive 0.2750 0.2241 D19-0.300 positive 0.3000 0.2362 D19-0.325 positive 0.3250 0.2530 D19-0.350 positive 0.3500 0.3078 D19-0.375 positive 0.3750 0.3103 D19-0.400 positive 0.4000 0.3277 D19-0.425 positive 0.4250 0.3472 D19-0.450 positive 0.4500 0.3787 D19-0.475 positive 0.4750 0.3919 D19-0.500 positive 0.5000 0.4156 D19-0.525 positive 0.5250 0.4327 D19-0.550 positive 0.5500 0.4640 D19-0.575 positive 0.5750 0.4798 D19-0.600 positive 0.6000 0.5154 D19-0.625 positive 0.6250 0.5406 D19-0.650 positive 0.6500 0.5359 D19-0.675 positive 0.6750 0.5388 D19-0.700 positive 0.7000 0.5457 D19-0.725 positive 0.7250 0.5634 D19-0.7363 positive 0.7363 0.5554 E2c-0.005 positive 0.0050 0.0033 E2c-0.010 positive 0.0100 0.0041 E2c-0.015 positive 0.0150 0.0371 E2c-0.020 positive 0.0200 0.0500 E2c-0.025 positive 0.0250 0.0740 E2c-0.030 positive 0.0300 0.0815 E2c-0.035 positive 0.0350 0.0885 E2c-0.040 positive 0.0400 0.0859 E2c-0.045 positive 0.0450 0.0961 E2c-0.050 positive 0.0500 0.1203 E2c-0.075 positive 0.0750 0.1333 E2c-0.100 positive 0.1000 0.1525 E2c-0.125 positive 0.1250 0.1676 E2c-0.150 positive 0.1500 0.1783 E2c-0.175 positive 0.1750 0.2136 E2c-0.200 positive 0.2000 0.2138 E2c-0.225 positive 0.2250 0.2539 E2c-0.250 positive 0.2500 0.3305 E2c-0.275 positive 0.2750 0.3979 E2c-0.300 positive 0.3000 0.4422 E2c-0.325 positive 0.3250 0.4868 E2c-0.350 positive 0.3500 0.5341 E2c-0.375 positive 0.3750 0.5800 E2c-0.400 positive 0.4000 0.5747 E2c-0.4122 positive 0.4122 0.5703 E6c-0.005 positive 0.0050 0.0165 E6c-0.010 positive 0.0100 0.0221 E6c-0.015 positive 0.0150 0.0206 E6c-0.020 positive 0.0200 0.0395 E6c-0.025 positive 0.0250 0.0451 E6c-0.030 positive 0.0300 0.0589 E6c-0.035 positive 0.0350 0.0643 E6c-0.040 positive 0.0400 0.0687 E6c-0.045 positive 0.0450 0.0750 E6c-0.050 positive 0.0500 0.0744 E6c-0.075 positive 0.0750 0.1185 E6c-0.100 positive 0.1000 0.1275 E6c-0.125 positive 0.1250 0.1787 E6c-0.150 positive 0.1500 0.2008 E6c-0.175 positive 0.1750 0.2179 E6c-0.200 positive 0.2000 0.2374 E6c-0.225 positive 0.2250 0.2570 E6c-0.250 positive 0.2500 0.3111 E6c-0.275 positive 0.2750 0.3204 E6c-0.300 positive 0.3000 0.3706 E6c-0.325 positive 0.3250 0.4481 E6c-0.350 positive 0.3500 0.4578 E6c-0.375 positive 0.3750 0.4920 E6c-0.400 positive 0.4000 0.5168 E6c-0.425 positive 0.4250 0.5272 E6c-0.450 positive 0.4500 0.5648 E6c-0.475 positive 0.4750 0.5723 E6c-0.500 positive 0.5000 0.6091 E6c-0.525 positive 0.5250 0.6031 E6c-0.5386 positive 0.5386 0.5896 sub-healthy-1 negative 0.0000 0.0187 sub-healthy-2 negative 0.0000 0.0122 sub-healthy-3 negative 0.0000 0.0193 sub-healthy-4 negative 0.0000 0.0179 sub-healthy-5 negative 0.0000 0.0040 sub-healthy-6 negative 0.0000 0.0188 sub-healthy-7 negative 0.0000 0.0155 sub-healthy-8 negative 0.0000 0.0157 sub-healthy-9 negative 0.0000 0.0151 sub-healthy-10 negative 0.0000 0.0148 sub-healthy-11 negative 0.0000 0.0099 sub-healthy-12 negative 0.0000 0.0241 sub-healthy-13 negative 0.0000 0.0136 sub-healthy-14 negative 0.0000 0.0129 sub-healthy-15 negative 0.0000 0.0020 sub-healthy-16 negative 0.0000 0.0050 sub-healthy-17 negative 0.0000 0.0128 sub-healthy-18 negative 0.0000 0.0087 sub-healthy-19 negative 0.0000 0.0084 sub-healthy-20 negative 0.0000 0.0012 sub-healthy-21 negative 0.0000 0.0067 sub-healthy-22 negative 0.0000 0.0218 sub-healthy-23 negative 0.0000 0.0208 sub-healthy-24 negative 0.0000 0.0138 sub-healthy-25 negative 0.0000 0.0227 sub-healthy-26 negative 0.0000 0.0079 sub-healthy-27 negative 0.0000 0.0178 sub-healthy-28 negative 0.0000 0.0262 sub-healthy-29 negative 0.0000 0.0157 sub-healthy-30 negative 0.0000 0.0195 sub-healthy-31 negative 0.0000 0.0075 sub-healthy-32 negative 0.0000 0.0011 sub-healthy-33 negative 0.0000 0.0114 sub-healthy-34 negative 0.0000 0.0045 sub-healthy-35 negative 0.0000 0.0143 sub-healthy-36 negative 0.0000 0.0131 sub-healthy-37 negative 0.0000 0.0168 sub-healthy-38 negative 0.0000 0.0065 sub-healthy-39 negative 0.0000 0.0026 sub-healthy-40 negative 0.0000 0.0028

TABLE S12 A panel of 77 genes for screening breast cancer samples. CDH1 ARID1A MAGI3 FLT3 SMARCB1 RNF43 FGFR2 CDKN2A ATR MDM2 GNA11 SMO APC MET HRAS AURKA MDM4 GNAQ VHL EGFR FGFR3 JAK2 BRCA1 KMT2C GNAS BRAF ZNRF3 ALK JAK3 BRCA2 NOTCH4 HNF1A KRAS ATM MAP2K1 NF1 CDKN1B TSC1 IDH1 NRAS PTEN MTOR NOTCH1 DOT1L TSC2 IDH2 PIK3CA CTNNB1 MAP2K4 RB1 ERBB3 ABL1 KDR PIK3R1 MLH1 MAP3K1 RET ESR1 CSF1R MPL SMAD4 ERBB2 AKT1 SRC GATA3 DDR2 NPM1 TP53 ERBB4 PDGFRA STK11 JAK1 EZH2 PTPN11 FBXW7 FGFR1 KIT

TABLE S13 Transcript expression data. sample source tissue size download URLs GTEx whole blood 337 https://toil.xenahubs.net/download/gtex_RSEM_isoform_fpkm.gz TCGA tumor of colorectal 372 https://toil.xenahubs.net/download/tcga_RSEM_isoform_fpkm.gz cancer (CRC)

TABLE S14 Information on all predictive features for colorectal cancer Feature ID MAE 59 86 475 703 760 790 0.017 70 256 268 322 379 903 0.019 72 86 703 760 790 900 0.019 70 78 268 322 364 475 0.020 86 553 703 760 790 900 0.020 59 86 703 760 790 900 0.020 72 86 760 790 900 905 0.020 256 268 322 379 475 553 0.020 70 268 322 364 571 903 0.021 70 161 268 322 571 903 0.021 161 268 322 359 553 903 0.021 86 703 760 790 900 905 0.021 78 268 284 322 571 903 0.021 256 268 284 322 359 379 0.021 115 161 268 744 903 905 0.021 70 78 268 284 322 903 0.021 161 268 284 359 553 903 0.021 70 115 268 322 571 903 0.021 284 355 379 475 571 788 0.021 70 268 284 322 571 903 0.021 59 78 126 154 181 639 0.021 86 703 760 788 790 900 0.021 70 161 181 322 480 903 0.021 59 86 703 760 790 905 0.021 124 181 256 485 744 905 0.021 70 161 268 284 322 903 0.022 70 115 161 268 359 903 0.022 115 161 268 553 884 905 0.022 124 161 268 553 673 905 0.022 70 268 284 322 364 903 0.022 59 124 126 153 161 250 0.022 70 124 161 268 322 903 0.022 115 161 181 553 673 905 0.022 161 268 322 359 553 571 0.022 124 163 268 485 553 673 0.022 70 268 571 839 903 905 0.022 78 268 284 322 884 903 0.022 268 322 359 379 475 553 0.022 124 181 485 571 673 744 0.022 268 284 322 553 884 903 0.022 78 115 124 268 322 903 0.022 124 284 475 480 673 788 0.022 126 568 604 714 777 830 0.022 70 161 268 284 903 905 0.022 59 86 553 703 760 790 0.022 268 322 379 475 553 905 0.022 67 124 161 181 284 673 0.022 268 359 379 475 553 905 0.023 70 268 284 322 884 903 0.023 115 284 359 485 571 777 0.023 268 284 359 379 475 553 0.023 268 322 777 788 884 903 0.023 70 181 322 475 480 884 0.023 78 161 258 234 322 903 0.023 115 161 268 284 903 905 0.023 115 124 181 284 447 485 0.023 115 181 284 571 824 903 0.023 70 124 161 268 673 903 0.023 67 124 181 485 673 744 0.023 67 124 181 673 830 839 0.023 70 268 284 322 673 903 0.023 70 124 161 268 903 905 0.023 70 161 268 839 903 905 0.023 70 115 124 268 903 905 0.023 59 86 703 760 788 790 0.023 39 447 466 595 604 639 0.023 124 161 181 256 673 744 0.023 70 470 480 485 639 858 0.023 70 115 181 475 571 884 0.023 268 359 379 475 553 788 0.023 70 115 268 379 571 900 0.023 70 124 161 181 903 905 0.023 72 154 284 777 788 884 0.024 124 161 268 553 903 305 0.024 336 540 632 714 793 874 0.024 70 181 336 830 839 884 0.024 70 115 124 268 571 903 0.024 2 256 336 529 632 682 0.024 161 256 268 336 475 905 0.024 379 553 571 788 858 900 0.024 268 284 322 673 788 903 0.024 115 124 161 181 284 447 0.024 70 268 284 788 903 905 0.024 115 284 480 485 529 777 0.024 359 475 553 571 788 900 0.024 70 161 181 571 884 903 0.024 161 181 744 884 903 905 0.024 70 161 181 284 884 903 0.024 115 124 268 322 379 673 0.024 268 284 322 788 884 903 0.024 82 217 477 487 629 717 0.024 268 359 379 475 571 788 0.024 161 268 284 322 673 903 0.024 126 466 470 639 793 858 0.024 2 39 256 395 619 839 0.024 124 126 161 181 284 673 0.024 2 115 324 181 359 830 0.025 359 379 475 553 571 900 0.025 124 161 181 673 744 830 0.025 70 151 268 284 673 903 0.025 124 181 256 359 485 830 0.025 124 181 364 673 788 903 0.025 115 161 181 359 485 673 0.025 480 485 673 721 744 858 0.025 70 475 571 788 900 905 0.025 284 379 475 788 900 905 0.025 78 153 322 568 830 884 0.025 70 379 475 571 788 900 0.025 124 161 181 284 364 673 0.025 115 124 161 181 673 744 0.025 2 337 384 395 839 899 0.025 161 256 268 359 379 573 0.025 284 322 788 884 903 905 0.025 115 161 268 284 673 903 0.025 364 410 525 542 793 839 0.025 70 115 124 161 181 905 0.025 124 268 284 322 788 903 0.025 115 154 359 480 485 830 0.025 78 154 364 542 619 796 0.025 84 336 359 466 632 858 0.025 359 379 475 553 788 884 0.025 379 553 571 788 900 905 0.025 72 126 204 542 714 796 0.025 78 124 181 359 485 830 0.025 181 256 359 485 777 830 0.025 268 359 379 475 788 884 0.025 115 124 161 268 903 905 0.025 78 115 154 364 604 830 0.025 359 379 475 553 571 788 0.025 181 256 485 555 673 744 0.025 124 181 256 284 673 830 0.025 115 126 161 284 903 905 0.025 78 154 364 485 568 830 0.025 39 256 525 568 619 839 0.025 115 154 181 256 485 905 0.026 181 202 284 322 673 884 0.026 78 204 364 525 542 632 0.026 181 284 322 673 777 884 0.026 115 161 181 673 744 884 0.026 364 563 619 830 858 884 0.026 284 322 571 788 884 903 0.026 181 284 322 480 903 905 0.026 115 124 161 181 284 673 0.026 32 122 202 286 487 594 0.026 115 161 268 322 884 903 0.026 72 153 247 250 591 594 0.026 70 115 161 268 234 903 0.026 70 181 478 721 744 884 0.026 115 124 181 673 744 830 0.026 70 124 181 788 903 905 0.026 284 359 379 475 553 571 0.026 78 154 542 568 721 830 0.026 78 126 256 522 542 639 0.026 161 268 284 322 359 903 0.026 124 161 268 322 379 673 0.026 67 332 455 580 704 904 0.026 268 322 359 571 788 903 0.026 2 256 464 540 568 874 0.026 154 480 485 568 673 744 0.026 124 161 268 673 788 903 0.026 70 395 410 540 702 874 0.026 161 268 322 364 673 903 0.026 124 181 256 359 744 830 0.026 181 284 322 485 721 903 0.026 59 336 470 632 721 858 0.026 39 256 337 407 702 839 0.026 67 124 181 284 364 903 0.026 359 619 721 744 830 884 0.026 181 284 322 359 485 884 0.026 268 284 322 359 379 903 0.026 124 181 284 359 364 485 0.026 268 379 475 571 788 900 0.026 70 124 126 256 470 830 0.026 2 115 154 604 619 830 0.026 115 154 359 480 721 777 0.026 153 256 336 359 410 639 0.026 84 359 604 619 830 858 0.026 39 204 632 793 858 901 0.026 67 78 124 126 256 364 0.026 322 359 379 475 788 884 0.027 59 161 181 673 744 884 0.027 181 364 673 721 744 903 0.027 181 284 322 485 673 777 0.027 78 204 632 682 721 858 0.027 161 181 322 673 744 884 0.027 115 124 161 181 673 905 0.027 70 364 480 542 619 721 0.027 70 379 475 788 900 905 0.027 268 322 359 379 673 903 0.027 96 122 202 447 675 695 0.027 59 78 115 525 619 744 0.027 322 359 379 553 571 788 0.027 59 124 161 181 322 903 0.027 78 154 250 478 777 796 0.027 322 359 379 475 571 788 0.027 284 359 379 475 553 788 0.027 154 181 284 322 673 777 0.027 124 268 359 379 475 571 0.027 161 268 284 322 884 903 0.027 70 480 542 639 682 721 0.027 161 181 202 284 884 903 0.027 78 124 161 268 284 903 0.027 78 124 181 673 744 830 0.027 115 322 604 744 777 830 0.027 70 124 181 256 284 903 0.027 124 359 379 475 788 905 0.027 139 250 336 364 542 796 0.027 322 359 480 673 721 744 0.027 154 364 480 485 542 619 0.027 78 126 364 632 777 796 0.027 59 639 682 793 796 858 0.027 204 478 542 639 721 793 0.027 67 468 487 721 780 899 0.027 451 522 525 542 619 793 0.027 126 161 181 673 903 905 0.027 39 237 384 702 727 796 0.027 124 161 368 571 673 903 0.027 124 161 181 359 485 744 0.027 126 154 466 639 682 858 0.027 115 410 525 744 777 830 0.027 59 161 181 202 480 744 0.027 379 475 553 571 788 900 0.027 35 39 153 464 540 796 0.027 161 181 485 673 744 884 0.027 59 73 126 153 154 884 0.027 126 336 348 466 721 852 0.027 115 124 480 673 744 905 0.027 115 181 485 673 744 839 0.027 78 126 154 485 568 777 0.027 78 182 284 322 485 777 0.027 78 154 181 284 485 777 0.027 322 359 475 553 571 788 0.027 59 161 268 322 364 903 0.027 2 39 337 702 766 899 0.027 204 364 542 619 714 796 0.027 70 379 475 571 900 905 0.027 67 153 429 540 568 874 0.027 359 379 475 788 884 905 0.027 59 124 161 181 673 903 0.027 78 154 364 568 777 830 0.027 70 115 124 268 485 903 0.027 359 379 475 571 788 905 0.027 72 109 202 348 410 473 0.027 256 447 468 469 568 717 0.028 18 217 391 455 480 717 0.028 268 284 379 475 788 900 0.028 42 407 522 568 721 896 0.028 70 72 542 639 744 796 0.028 70 126 181 478 571 839 0.028 70 126 470 480 639 858 0.028 59 124 161 359 485 830 0.028 2 18 410 525 632 839 0.028 59 475 553 673 703 788 0.028 204 256 525 568 682 793 0.028 181 284 322 485 777 884 0.028 70 153 322 568 830 884 0.028 115 124 447 702 830 858 0.028 78 126 154 639 793 858 0.028 67 451 455 470 568 766 0.028 395 540 632 714 793 874 0.028 39 204 480 542 632 793 0.028 59 379 475 571 673 788 0.028 379 475 553 788 884 905 0.028 78 115 256 470 788 830 0.028 161 268 673 788 903 905 0.028 124 181 322 364 485 673 0.028 359 379 475 553 571 884 0.028 126 529 632 639 793 858 0.028 18 466 639 744 858 884 0.028 268 379 475 788 900 905 0.028 410 466 470 480 525 744 0.028 78 115 154 485 744 830 0.028 115 154 181 359 485 903 0.028 447 468 529 704 841 867 0.028 39 337 714 766 793 842 0.028 70 256 336 395 632 839 0.028 161 268 284 485 673 903 0.028 78 154 181 485 777 839 0.028 139 384 455 525 568 830 0.028 78 154 359 455 480 830 0.028 154 395 466 555 639 796 0.028 67 197 270 429 632 761 0.028 78 154 322 364 568 777 0.028 32 179 473 753 780 904 0.028 115 124 161 268 364 839 0.028 72 154 284 485 673 777 0.028 154 359 480 485 673 830 0.028 204 466 470 480 639 858 0.028 59 126 410 619 639 744 0.028 161 268 284 322 379 903 0.028 256 407 473 555 824 874 0.028 2 522 525 529 721 793 0.028 359 379 475 553 571 673 0.028 78 256 632 682 777 858 0.028 67 115 124 256 284 485 0.028 59 480 485 744 830 884 0.028 78 115 153 322 721 777 0.028 153 525 542 714 721 796 0.028 379 475 553 571 788 884 0.028 78 115 154 181 284 777 0.028 115 284 485 571 673 884 0.028 115 284 485 529 777 884 0.028 126 466 470 714 796 858 0.028 84 204 466 470 604 858 0.028 115 154 284 364 571 884 0.028 70 115 181 478 744 777 0.028 181 336 480 702 721 744 0.028 115 154 673 744 830 858 0.028 322 359 379 475 553 788 0.028 78 115 154 256 777 830 0.028 78 250 256 364 410 796 0.028 204 364 470 568 721 830 0.029 70 364 470 480 639 793 0.029 78 204 542 632 766 858 0.029 78 126 153 154 529 830 0.029 115 124 126 161 485 555 0.029 447 451 522 721 793 842 0.029 59 78 126 154 744 777 0.029 59 126 714 839 874 884 0.029 18 256 522 555 632 682 0.029 115 480 485 619 744 830 0.029 359 379 475 553 673 788 0.029 466 528 540 717 824 904 0.029 264 270 412 447 842 856 0.029 395 451 470 568 604 656 0.029 39 337 384 466 639 824 0.029 540 604 632 688 780 904 0.029 364 485 542 796 839 905 0.029 379 475 571 788 900 905 0.029 79 96 217 336 717 753 0.029 126 154 256 359 830 884 0.029 78 126 154 571 639 858 0.029 379 475 673 788 884 905 0.029 332 580 704 796 841 904 0.029 96 204 256 384 466 470 0.029 115 124 161 181 485 673 0.029 78 153 410 542 632 766 0.029 124 268 379 571 788 900 0.029 78 154 485 744 777 858 0.029 18 139 325 407 466 632 0.029 115 154 364 480 619 858 0.029 337 429 555 714 822 824 0.029 2 70 395 540 632 682 0.029 161 181 284 485 673 721 0.029 79 336 455 466 632 702 0.029 72 96 468 477 590 855 0.029 359 379 475 553 788 905 0.029 161 268 788 884 903 905 0.029 2 395 540 632 714 874 0.029 249 337 522 704 749 780 0.029 2 33 337 478 525 540 0.029 79 204 429 522 525 529 0.029 35 270 293 555 632 896 0.029 153 154 480 568 682 884 0.029 284 485 571 673 777 884 0.029 115 124 161 268 364 903 0.029 126 395 451 542 714 793 0.029 18 153 447 528 632 904 0.029 359 379 475 788 900 905 0.029 88 293 412 428 632 685 0.029 412 404 466 632 704 842 0.029 35 79 249 704 780 896 0.029 78 115 126 154 256 777 0.029 4 85 202 217 249 465 0.029 153 568 604 714 727 766 0.029 379 475 553 571 673 788 0.029 2 391 466 632 735 858 0.029 78 154 364 604 777 858 0.029 35 67 270 384 412 727 0.029 2 18 96 153 555 842 0.029 67 522 529 540 688 842 0.029 202 204 466 470 639 682 0.029 18 204 384 466 639 899 0.029 249 395 487 594 841 899 0.029 70 153 336 455 568 721 0.029 67 336 429 451 470 480 0.029 124 161 268 364 571 903 0.029 59 115 126 485 744 830 0.029 322 359 379 475 553 571 0.029 78 115 124 256 322 485 0.029 67 217 230 249 465 487 0.029 466 528 540 555 717 824 0.030 39 204 525 542 619 793 0.030 2 256 451 568 824 874 0.030 202 256 469 473 528 717 0.030 115 181 256 284 364 903 0.030 176 266 407 447 522 727 0.030 39 256 395 447 555 748 0.030 115 124 161 268 744 830 0.030 67 395 412 451 464 727 0.030 39 337 466 766 842 899 0.030 154 181 322 673 788 884 0.030 2 126 359 777 796 858 0.030 70 284 322 384 571 903 0.030 78 115 153 154 721 777 0.030 67 75 217 465 511 899 0.030 42 391 407 451 466 717 0.030 18 153 204 542 568 796 0.030 124 181 284 485 777 884 0.030 256 470 632 766 777 796 0.030 126 395 447 632 714 793 0.030 407 466 522 528 604 639 0.030 78 124 181 364 485 673 0.030 78 124 364 542 639 714 0.030 379 475 553 571 788 905 0.030 39 153 395 540 721 727 0.030 70 395 470 485 766 899 0.030 39 204 395 528 604 839 0.030 79 337 395 528 555 727 0.030 379 475 571 673 788 884 0.030 379 475 571 673 788 905 0.030 153 154 480 542 721 793 0.030 35 391 540 586 717 793 0.030 475 553 571 788 884 905 0.030 275 359 485 619 796 830 0.030 18 122 202 270 688 761 0.030 67 72 410 429 704 901 0.030 82 154 364 793 796 858 0.030 124 268 379 553 788 805 0.030 466 528 568 721 727 766 0.030 35 57 632 634 655 904 0.030 18 154 470 540 639 796 0.030 57 82 202 410 594 632 0.030 179 249 270 293 337 515 0.030 204 604 619 714 777 796 0.030 70 126 364 542 619 796 0.030 217 467 477 478 717 841 0.030 18 67 487 529 701 904 0.030 2 115 181 256 744 777 0.030 18 395 466 555 721 727 0.030 204 480 542 682 721 753 0.030 72 179 247 594 685 841 0.030 42 122 217 270 822 899 0.030 359 379 475 553 571 905 0.030 115 268 284 487 830 900 0.024 Columns Feature ID: feature index (see Table S3 for feature details) MAE: mean absolute error between observed and calculated ctDNA fractions from 344 samples

TABLE S15 Information on predictive features for colorectal cancer ID Transcript Gene Chr Site Region Group FPKM_(blood) FPKM_(tumor) 2 ENST00000027335.7 CDH17 8 95220815 promoter tumor 0.00 149.83 4 ENST00000162330.9 BCAR1 16 75285507 promoter tumor 0.00 16.86 18 ENST00000245451.8 BMP4 14 54423529 promoter tumor 0.00 16.43 32 ENST00000264144.4 LAMC2 1 183155423 promoter tumor 0.01 31.46 35 ENST00000267101.7 ERBB3 12 56473645 promoter tumor 0.00 40.98 39 ENST00000270560.3 TM4SF5 17 4675187 promoter tumor 0.00 18.39 42 ENST00000278937.6 MPZL2 11 118134997 promoter tumor 0.37 17.05 57 ENST00000300119.7 MYO1A 12 57443901 promoter tumor 0.00 15.11 59 ENST00000300557.2 PRR15L 17 46035244 promoter tumor 0.03 96.21 67 ENST00000310836.10 UGT8 4 115519611 promoter tumor 0.04 14.08 70 ENST00000311620.6 ANKS4B 16 21244986 promoter tumor 0.00 10.61 72 ENST00000317508.10 PRSS8 16 31147083 promoter tumor 0.11 143.22 75 ENST00000318443.9 CD276 15 73976554 promoter tumor 0.00 11.45 78 ENST00000322536.7 DDX10 11 108535752 promoter tumor 0.75 10.84 79 ENST00000324038.6 FAM101A 12 124773710 promoter tumor 0.00 10.08 82 ENST00000326587.11 MAGED1 X 51636698 promoter tumor 0.60 16.14 84 ENST00000331243.4 FAM84A 2 14772824 promoter tumor 0.01 33.07 85 ENST00000331595.8 BGN X 152760397 promoter tumor 0.60 74.92 86 ENST00000332149.9 TMPRSS2 21 42880086 promoter tumor 0.02 43.57 88 ENST00000334047.11 F3 1 95007356 promoter tumor 0.08 13.07 96 ENST00000352551.9 UBE2C 20 44441313 promoter tumor 0.00 10.99 109 ENST00000358867.10 TMEM126B 11 85339629 promoter tumor 0.47 17.68 115 ENST00000361084.9 RAB25 1 156030951 promoter tumor 0.07 131.50 122 ENST00000367284.9 ELF3 1 201979645 promoter tumor 0.02 50.55 124 ENST00000367976.3 CTGF 6 132272513 promoter tumor 0.32 44.18 126 ENST00000368554.8 PRAP1 10 135122914 promoter tumor 0.00 32.41 139 ENST00000374214.3 UQCC2 6 33679504 promoter tumor 1.00 17.77 153 ENST00000380071.7 RFC3 13 34392186 promoter tumor 0.48 15.11 154 ENST00000381134.7 ARSE X 2882311 promoter tumor 0.00 24.51 161 ENST00000394201.8 SCOC 4 141294797 promoter tumor 0.53 14.61 176 ENST00000419308.6 FOXA2 20 22565101 promoter tumor 0.00 13.51 179 ENST00000425042.6 HID1 17 72968829 promoter tumor 0.23 13.99 181 ENST00000427250.5 LSR 19 35739905 promoter tumor 0.00 13.66 197 ENST00000463201.2 PRAP1 10 135164879 promoter tumor 0.00 54.46 202 ENST00000473336.5 RAB25 1 156031174 promoter tumor 0.00 17.65 204 ENST00000478194.1 FERMT1 20 6074819 promoter tumor 0.00 27.00 217 ENST00000497734.5 SRC 20 35973088 promoter tumor 0.00 12.44 230 ENST00000532203.1 MRPL17 11 6704547 promoter tumor 0.65 21.73 247 ENST00000554989.1 CKB 14 103987659 promoter tumor 0.75 83.82 249 ENST00000558580.1 SORD 15 45328434 promoter tumor 0.95 15.73 250 ENST00000561504.1 ADIRF 10 88728247 promoter tumor 0.75 46.05 256 ENST00000588605.5 C19orf33 19 38794804 promoter tumor 0.22 18.46 264 ENST00000597153.5 LGALS4 19 39303585 promoter tumor 0.00 20.51 266 ENST00000600324.5 STAP2 19 4338818 promoter tumor 0.02 13.85 268 ENST00000605618.5 LSR 19 35739922 promoter tumor 0.22 31.85 270 ENST00000612794.1 GPX2 14 65409623 promoter tumor 0.00 23.73 275 ENST00000619895.4 TMC4 19 54676865 promoter tumor 0.35 33.05 284 ENST00000234347.9 PRTN3 19 840960 promoter blood 13.78 0.00 286 ENST00000244709.8 TREM1 6 41254457 promoter blood 67.12 0.63 293 ENST00000279452.10 CD44 11 35198175 promoter blood 10.76 0.00 322 ENST00000355524.7 FCAR 19 55385736 promoter blood 53.04 0.07 325 ENST00000356864.3 TNFRSF10C 8 22960103 promoter blood 108.86 0.56 332 ENST00000367568.4 STX11 6 144471663 promoter blood 24.42 0.79 336 ENST00000368737.4 S100A12 1 153348125 promoter blood 1099.02 0.31 337 ENST00000371806.3 FCN1 9 137809809 promoter blood 379.64 0.88 348 ENST00000380299.3 HBD 11 5255878 promoter blood 138.84 0.07 359 ENST00000398421.6 NCF1 7 74188358 promoter blood 11.04 0.04 364 ENST00000413580.5 PHOSPHO1 17 47308128 promoter blood 42.76 0.05 379 ENST00000454703.6 ACSL1 4 185747273 promoter blood 35.07 0.78 384 ENST00000465984.5 SLC11A1 2 219246911 promoter blood 10.54 0.03 391 ENST00000480395.5 TRIM22 11 5717722 promoter blood 17.36 0.70 395 ENST00000485743.1 HBB 11 5248302 promoter blood 128.52 0.00 407 ENST00000496823.1 BCL6 3 187463247 promoter blood 21.33 0.20 410 ENST00000509314.5 FBXL5 4 15661487 promoter blood 10.24 0.00 412 ENST00000510784.6 FAM65B 6 25042396 promoter blood 61.47 0.19 428 ENST00000535669.6 CD37 19 49838684 promoter blood 33.70 0.19 429 ENST00000539932.5 SLC11A1 2 219246926 promoter blood 50.32 0.02 447 ENST00000576628.1 ACAP1 17 7239916 promoter blood 20.20 0.18 451 ENST00000585901.6 TYROBP 19 36399149 promoter blood 13.40 0.19 455 ENST00000588673.3 OAZ1 19 2270290 promoter blood 24.28 0.69 464 ENST00000595840.1 LRRC25 19 18508421 promoter blood 36.84 0.88 465 ENST00000596426.5 CD37 19 49838691 promoter blood 55.55 0.57 466 ENST00000596764.5 VAV1 19 6772739 promoter blood 12.25 0.59 467 ENST00000597852.5 CD37 19 49838675 promoter blood 13.98 0.20 468 ENST00000598034.5 GMFG 19 39826646 promoter blood 43.77 0.45 469 ENST00000599180.2 FFAR2 19 35939203 promoter blood 24.79 0.00 470 ENST00000599716.5 SHKBP1 19 41082793 promoter blood 10.66 0.22 473 ENST00000602185.5 GMFG 19 39826645 promoter blood 14.09 0.00 475 ENST00000605039.5 BIN2 12 51717938 promoter blood 11.02 0.11 477 ENST00000612844.4 FOLR3 11 71846756 promoter blood 13.11 0.00 478 ENST00000615439.4 RASGRP4 19 38916945 promoter blood 10.11 0.00 480 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 0.07 485 ENST00000027335.7 CDH17 8 95220711 junction tumor 0.00 149.83 487 ENST00000162330.9 BCAR1 16 75285369 junction tumor 0.00 16.86 511 ENST00000262753.8 POF1B X 84634644 junction tumor 0.02 40.41 515 ENST00000264144.4 LAMC2 1 183155566 junction tumor 0.01 31.46 522 ENST00000270560.3 TM4SF5 17 4675394 junction tumor 0.00 18.39 525 ENST00000278937.6 MPZL2 11 118134811 junction tumor 0.37 17.05 528 ENST00000290913.7 CHCHD6 3 126423242 junction tumor 0.65 15.07 529 ENST00000291525.11 TFF3 21 43735403 junction tumor 0.00 209.02 540 ENST00000300119.7 MYO1A 12 57443671 junction tumor 0.00 15.11 542 ENST00000300557.2 PRR15L 17 46035023 junction tumor 0.03 96.21 553 ENST00000311620.6 ANKS4B 16 21245222 junction tumor 0.00 10.61 555 ENST00000317508.10 PRSS8 16 31146735 junction tumor 0.11 143.22 568 ENST00000332149.9 TMPRSS2 21 42880008 junction tumor 0.02 43.57 571 ENST00000334869.8 LGMN 14 93214834 junction tumor 0.94 45.73 580 ENST00000354900.7 LSR 19 35740034 junction tumor 0.75 31.22 586 ENST00000357166.10 ZDHHC9 X 128977672 junction tumor 0.29 20.11 590 ENST00000358867.10 TMEM126B 11 85339732 junction tumor 0.47 17.68 591 ENST00000360325.11 CLDN7 17 7165140 junction tumor 0.09 133.65 594 ENST00000360779.3 SDCBP2 20 1309729 junction tumor 0.00 17.84 595 ENST00000361084.9 RAB25 1 156031234 junction tumor 0.07 131.50 604 ENST00000367976.3 CTGF 6 132272247 junction tumor 0.32 44.18 619 ENST00000374214.3 UQCC2 6 33679326 junction tumor 1.00 17.77 629 ENST00000379742.4 POSTN 13 38172745 junction tumor 0.01 11.69 632 ENST00000381134.7 ARSE X 2882265 junction tumor 0.00 24.51 634 ENST00000389614.5 GPX2 14 65409223 junction tumor 0.10 652.10 639 ENST00000394201.8 SCOC 4 141294871 junction tumor 0.53 14.61 655 ENST00000425042.6 HID1 17 72968686 junction tumor 0.23 13.99 656 ENST00000425340.2 FUT2 19 49199346 junction tumor 0.02 13.10 673 ENST00000472782.1 ATP5G3 2 176046384 junction tumor 0.62 10.87 675 ENST00000478194.1 FERMT1 20 6074721 junction tumor 0.00 27.00 682 ENST00000494801.5 TCEAL4 X 102840552 junction tumor 0.60 13.59 685 ENST00000497734.5 SRC 20 35973290 junction tumor 0.00 12.44 688 ENST00000514985.5 SEPP1 5 42811938 junction tumor 0.59 49.95 695 ENST00000528430.2 PPP1R16A 8 145726677 junction tumor 0.92 22.33 701 ENST00000542056.1 GPRC5A 12 13044598 junction tumor 0.00 23.91 702 ENST00000543445.5 LDHA 11 18416188 junction tumor 0.00 71.47 703 ENST00000543623.5 PLCD3 17 43192462 junction tumor 0.27 14.58 704 ENST00000546314.5 STARD10 11 72493311 junction tumor 0.00 31.66 714 ENST00000559087.5 BMP4 14 54423477 junction tumor 0.00 13.08 717 ENST00000581920.1 TYMS 18 667752 junction tumor 0.88 11.79 721 ENST00000588605.5 C19orf33 19 38794923 junction tumor 0.22 18.46 727 ENST00000597153.5 LGALS4 19 39303482 junction tumor 0.00 20.51 735 ENST00000619895.4 TMC4 19 54676734 junction tumor 0.35 33.05 744 ENST00000234347.9 PRTN3 19 841069 junction blood 13.78 0.00 748 ENST00000246549.2 FFAR2 19 35942667 junction blood 58.85 0.34 749 ENST00000246657.2 CCR7 17 38721652 junction blood 11.89 0.75 753 ENST00000279452.10 CD44 11 35198287 junction blood 10.76 0.00 760 ENST00000297239.10 SYTL3 6 159082417 junction blood 10.79 0.54 761 ENST00000299663.7 CLEC4E 12 8693357 junction blood 29.27 0.20 766 ENST00000310544.8 PHOSPHO1 17 47307830 junction blood 30.92 0.08 777 ENST00000343534.9 C1orf162 1 112016652 junction blood 37.68 0.74 780 ENST00000354352.9 SLC11A1 2 219247098 junction blood 111.80 0.63 788 ENST00000367025.7 TRAF3IP3 1 209929654 junction blood 17.52 0.64 790 ENST00000367535.7 NCF2 1 183559291 junction blood 75.23 0.98 793 ENST00000368015.1 ARHGAP30 1 161039410 junction blood 20.61 0.58 796 ENST00000371806.3 FCN1 9 137809615 junction blood 379.64 0.88 822 ENST00000422400.6 VNN2 6 133078810 junction blood 14.59 0.10 824 ENST00000433194.6 CDK5RAP2 9 123165594 junction blood 22.55 0.52 830 ENST00000454703.6 ACSL1 4 185747070 junction blood 35.07 0.78 839 ENST00000480395.5 TRIM22 11 5717885 junction blood 17.36 0.70 841 ENST00000483750.5 WAS X 48542374 junction blood 34.49 0.17 842 ENST00000485743.1 HBB 11 5248160 junction blood 128.52 0.00 852 ENST00000496823.1 BCL6 3 187463198 junction blood 21.33 0.20 855 ENST00000509314.5 FBXL5 4 15661350 junction blood 10.24 0.00 856 ENST00000509339.1 MXD3 5 176734782 junction blood 30.07 0.08 858 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 0.10 867 ENST00000540998.5 CDC42SE1 1 151031955 junction blood 10.52 0.00 874 ENST00000553070.5 NFE2 12 54694585 junction blood 23.61 0.00 884 ENST00000578402.5 LIMD2 17 61777729 junction blood 31.49 0.77 896 ENST00000595840.1 LRRC25 19 18508263 junction blood 36.84 0.88 899 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 0.00 900 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 0.22 901 ENST00000600626.1 C5AR2 19 47840426 junction blood 12.99 0.11 903 ENST00000605039.5 BIN2 12 51717806 junction blood 11.02 0.11 904 ENST00000611028.2 FOLR3 11 71846814 junction blood 11.13 0.00 905 ENST00000615439.4 RASGRP4 19 38916709 junction blood 10.11 0.00 Columns ID: feature index, same as Table S3 Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood FPKM_(tumor): FPKM value in tumor of colorectal cancer

TABLE S16 Information on additional predictive pan-cancer features Feature ID MAE 34 41 73 83 90 123 294 415 452 742 0.024 34 41 73 83 90 123 126 294 415 667 0.025 34 41 83 90 123 126 259 294 415 867 0.025 34 41 83 90 123 2

4 415 452

7 789 0.026 41 73 83 90 123 294 376 415 452 742 0.026 34 41 73 83

0 123 12

 29

4 415 78

0.026 34 64 135 201 27

 415 653 735 772 778 0.026 41 73 83 90 123 12

 294 37

 415 452 0.026 34 52 201 415 653 6

 735 7

3 772 77

0.026 41 73 83 90 123 12

 294 452 634 667 0.027 41 73 83 90 123 12

 294 415

34

67 0.027 41 7

 83 90 123 12

 294 37

 415

67 0.027 34 41 73 83 90 123 128 294 376 415 0.027 41 83 90 123 126 294 376 415 634 667 0.027 41

3 90 123 126 294 415

34 667 742 0.027 41 73 83 90 123 294 37

 452 634

67 0.027 41 73 83

0 123 128 294 452

67 78

0.028 41 73 83

0 123 12

 294 452 742 78

0.029 41

3 90 123 126 25

 2

4 452 667 742 0.029 41 73 83 90 123 12

 25

 294 421 452 0.029 41 73 83

0 123 12

 25

 2

4 378 415 0.029 41 73 83

0 123 12

 294 37

 452 742 0.029 97 137 205 454 634 653

67 680 778 787 0.029 41 7

 83 90 123 126 25

 27

 2

4 667 0.029 34 41 73 83 90 123 126 294 452 7

0.030 34 41 73 83 90 123 259 294 452 667 0.030 34 41 73 83 90 123 126 259 294 452 0.030 34 41 73 83 90 123 126 294 376 452 0.030 41 83 90 12

 259 294 415

34 667 742 0.030 41 83 90 123 2

 415

34

7 742 789 0.030 41 73 83 90 123 294 376 452

7 789 0.030 41 73 83 90 123 12

 259 294 376 452 0.030 41 73 83 90 123 259 294 37

 634

7 0.030 34 41 73 83 90 123 126 135 2

4 376 0.030 97 137 201 23

 278 348 415 454 772 778 0.031 41 73 83 90 123 128 294 37

 452 789 0.031 41 73 83

0 123 128 249 37

 634 667 0.031 41 73 83

0 123 12

 2

4 376 421 742 0.031 34 41 73 83 90 123 12

 294 376 667 0.031 34 41 83

0 123 12

 2

4 37

 

7 742 0.031

 34 8

 135 278 428 621

80 7

8 78

0.031 41 73 83

0 123 12

 2

4

34

7 78

0.032 73

3 90 123 126 13

 259 294 376 452 0.032 34 13

 236 278 428

21

0 7

3 7

 78

0.032

2 137 236 258 288 304 338 388 674 778 0.032 41 73 83

0 123 12

 2

4

34 667 742 0.032 34 137 201 23

 242 278 415 735 772 778 0.032 41 7

 83

0 123 12

 2

4 37

 

7 742 0.032 41 73 83

0 123 12

 259 294 37

 

67 0.032 41 73 83

0 123 126 294 6

7 742 789 0.032 34 89 135 205 242 428 621 680 768 789 0.032 34 41 73 83

0 123 12

 294 667 742 0.032 34 41 73 83

0 123 12

 294

67 7

0.032 34 37 52 135 201 23

 242 415 735 772 0.032 41 78 83 90 123 126 294 378

87 789 0.032 34 41 73 83 90 123 126 294 634 6

7 0.032 34 73 123 135 278 428 621 630 788 789 0.032 37 52 64 97 201 205 242 421 454 772 0.032 89 428 44

 454 834 667 680 742 768 789 0.032 8 52 135 25

 304 314 33

 454 666 778 0.032 34 89 135 278 428 621

80 768 772 789 0.032 34 41 73 83 90 132 12

 294 742 789 0.032 34 89 135 242 27

 428 521 680 768 789 0.033 34 41 73 83 90 123 12

 259 294 6

7 0.033 97 311 42

 454 621 634 667 680 742 768 0.033 34 73 135 137 421 428 621 680 768 772 0.033 34 41 83 90 123 126 2

4 667 742 789 0.033 34 41

3 90 123 126 2

4

34

7 789 0.033 15 29 89 152 288 2

 357 388 674 735 0.033 37 64 97 201 236 242 453 454 735 772 0.033 62 64 201 236 242 25

 388 421

21 772 0.033 34 41 73 83

0 123 1

 279 2

4 376 0.033 34 41 73 83

0 123 126 2

9 2

4 7

0.033

9 242 278 428

61 621 680 742 768 789 0.033 34 41 73

3 90 123 12

 294 37

 789 0.033 34 52 201 236 242 288 415 453 742 772 0.033 34 41 7

 83

0 123 126 2

 2

4 37

0.033 52 258 259 304 357 388 402 44

 

0

74 0.033

 34 89 135 238 242 428 742 788 789 0.033 41 83

0 12

 126 2

9 294 634 6

7 789 0.033 34 41 83 90 12

 126 294 376 742 789 0.033 9 52 201 28

 357 388 45

 547 630 674 0.033 8 152 259 2

9 309 435 544 735 775 778 0.033 73 137 415 421 428 454 621 634

7

0 0.033 9 37

4 201 236 258 415 674 735 778 0.034 41 73 83

0 123 294 6

4

7 742 78

0.034 15 29 127 206 302 30

 388 402

44 655 0.034 41 83

0 123 126 2

4

4

7 742 789 0.034 34 89 135 242 278 428

80 742 768 789 0.034 37 20

 236

02 311 338 454 621 666 742 0.034 41 73 83 90 123 126 2

4 376 742 789 0.034 37 64 201 206 236 258 338 415 666 763 0.034 41

3 90 123 12

 25

 294

34

7 742 0.034 278 376 428 454 4

8 621

34 680 768 789 0.034 41 73 83 90 123 126 259 294 742 789 0.034 8 126 135 152 20

 29

 30

 357 775 778 0.034

 242 311 428 454 634 6

0 742 768 789 0.034 9 52 135 242 259 357 388 3

2 43

 745 0.034

 52

4 89 236 258 288 338 376 435 0.034 52 73 201 242 302 454 621 666 73

 772 0.034 52 64 201 236 242 311 454 6

 742 772 0.034 9 89 258 259 288 302 3

8

21 630 674 0.034 37 64 258 314 338 454 630 686 763 787 0.034 13

 201 23

 242 278 304 645 6

3 772 778 0.034

9 135 137 20

 311 428 4

4 680 7

8 789 0.034 73 137 278 421 42

 454

21 634

0 768 0.034 52

4 137 20

 311 428 454 6

0 788 789 0.034 34 137 415 421 428

21 634

57

80 7

0.034 34 8

 135 27

 428 680 742 763 768 789 0.034 171 2

9 30

 408 544 608

44 645 666 724 0.034 8 29 52 2

8 304 338 402

07 630 655 0.034 18 29 299 357 415 453 630 674 682 766 0.034 9 29 152 23

 258 259 288 304 3

8 547 0.034 89 20

 428 454 634 653

7 680 768 789 0.034 127 137 20

 30

 402 412 415

53 655 786 0.034 41 73 83

0 12

 12

 2

 2

4 376 742 0.034 9 259 288 2

 357 388 547 630 655 674 0.034

4 137 284 304 621 634

45 6

3 772 778 0.034 152 357 38

 415 435 544 674 735 768 778 0.034 34 73 97 135 278 421 428 763 768 772 0.034

9 20

 278 311 428 454

34 680 788 789 0.034

 34 97 137 201 236 242 735 772 778 0.035 89 152 201 206 288 338 37

 392

5 775 0.035 37 201 23

 242 304 376 621 634

67 742 0.035 29 52 89 152 259 288 299 309 357 388 0.035 34 89 135 137 278 428 621 680 768 772 0.035 8 52 30

 435 544 607

30 735 775 778 0.035 8 29 52 236 357 388 435 4

3 454 674 0.035 52 152 205 2

8 388 630 735 745 778 787 0.035 73 135 242 278 421 428 454 621

0 768 0.035 29 89 135 152 258 331 482 547

34 742 0.035 52 174 331 338 435 454 4

 544

21 634 0.035 34 135 137 242 275 415 428 621 680 7

0.035 34 135 242 278 311 415 428 621 634 680 0.035 52 20

 258 288 296 338 403 435 547 65

0.035 205 278 376 42

 454 621

34

80 768 788 0.035 208 376 42

 454 621 634

67 6

0 768 789 0.035 34 89 205 278 428 621 634

0 7

 789 0.035 15 29 170 171 2

9 402 6

8

82 766 787 0.035 34 89 135 23

 278 311 428 44

 768 789 0.035 170 2

2 296 412 435 60

 644 703 708 7

0.035 37

4 152 201 205 242 302 454 6

 742 0.035 37 52

4 73 201 242 2

 421 674 772 0.035 170 296 302 40

 416 429 450 607 636 708 0.035 37 52 201 205 236 242 387 735 745 772 0.035

 37 52 64 135 242 304 621 742 772 0.035 34 89 135 137 205 27

 428 763 7

 789 0.035 52 64 126 201 205 288 415 454 742 772 0.035 137 201 242 259 288 421 454

21

80 772 0.035 89 135 20

 236 25

 338 357 435 547 778 0.035 29 52 201 25

 357 38

 402 454 544 807 0.035 8 37

4 236 258 304 338 3

7 376 5

4 0.036 29 127 306 3

 402 412 544 607 6

3

55 0.036 37 97 2

 242 278 311 454

34 735 772 0.036 15 89 152 206 259 28

 357 388 482 724 0.036 34 152 201 242 258 25

 288 2

 547 6

0.036 34 1

5 137 201 242 278 314 735 772 77

0.036 152 171 30

 402 544 60

 653 655 766 775 0.036 89 135 428 621 634 667 680 742 768 78

0.036 1

7 201 205 311 415 421 454 621 666 772 0.036 8 201 236 242 304 621 687 674 772 778 0.036 137 20

 2

 357 388 435 544 653 6

 778 0.036

 37

4 201 205 206 259 3

7 630 735 0.036 37 52

4 201 242 338 421 4

4 735 772 0.036 73 278 421 428 454

21 634 680 742 7

0.036 20

 262 311 33

 357 415 43

 482

44 778 0.036 89 201 23

 242 259 278 735 7

8 772 778 0.036 9 52

4 201 242 25

 278 304 3

7 778 0.036 9 13

 137 236 258 388 482 542 594 621 0.036 25

 338 3

7 376 388 435 45

 482 544 77

0.036 9 29 288 298 2

 388 402 4

3 630 775 0.036 211 306 37

 408 4

0 544

45 655 708 724 0.036 89 135 428 454 634

67 680 742 768 789 0.036 137 311 428 454 498 621

34

67 680 742 0.036 29 127 308 357 376 402 435 544

55 76

0.036 89 137 125 2

 37

 388 544 674 708 77

0.036 205 376 428 454 4

8 621

34

67 680 768 0.036 37

4 259 338 376 454

4

30

6 763 0.036 37 84 201 20

 2

 311 454

6 742 772 0.036 8 52 135 201 27

 367 376 7

 772 778 0.036 13

 205 278 428 454 621

34 6

0 7

 7

9 0.036 137 242 278 376 428 454

34 6

0 768 78

0.036 37 2

6 242 258 311 338 454 621

6 742 0.036 29

9 152 299 357 388 392 43

 544 594 0.036 89 205 278 428 454 634 680 742 768 78

0.036 34 52 201 20

 236 242 415 653 735 772 0.036 9 29 135 152 258 304 388 542 594 630 0.036 89 201 288 357 37

 388 392 402 6

 775 0.036 41 73 83 90 123 259 294 687 742 789 0.036 127 29

 306 357 388 435 544 608 6

 775 0.036 8 29 64 89 152 205 288 338 454 68

0.036 34 135 137 205 242 428 621 680 768 789 0.037 205 278 311 428 454 621 634 680 7

8 789 0.037 64 137 278 288 415 453 645 742 772 778 0.037 37 52 84 23

 242 258 421 621 674 772 0.037 73 137 242 278 428 454 634 680 768 789 0.037 29 52 259 288 338 357 388 45

 547 674 0.037 12

 127 170 171 298 65

 

66 724 766 77

0.037 89 137 20

 428 4

4 621 667 680 742 789 0.037 9 37 52

7 236 242 402 621 667 772 0.037 29 135 1

2 201 258 415 630 735 772 778 0.037 9 37 52

9 201 258

94 630 735 778 0.037 8 29 152 288 2

9 3

7 388 435 482 778 0.037 34 8

 205 278 311 425 6

0 742 7

 78

0.037 37 52 64 201 205 236 311 348 742 772 0.037 29 2

6 2

9 304 3

8 402 412 453

6 735 0.037 37 64 201 205 415 594 630 6

 735 78

0.037 37 52 64 201 236 242 259 367 735 772 0.037 52 201 258 288 357 388 402 547 607 653 0.037 12

 170 299 393 412 435 645 717 735 76

0.037 152 206 296 41

 435 4

0 63

 6

 708 76

0.037 8 52 152 201 299 3

7 43

 745 766 778 0.037 15 8

 127 142 288 311 388 416 724 778 0.037 8 52

 135 235 258 304 338 547 674 0.037 37 52

 258 314 338 421 5

4 6

0 674 0.037 8 37 64 242 278 304 367 421 772 778 0.037 8 37 135 208 258 259 304 314 338

6 0.037 89 242 278 311 428 454 621 680 7

 789 0.037 29 127 171 299 308 357 402 644 6

 7

0.037

 34 37 64 201 20

 634 653 738 772 0.037 37 52 278 314 338 388 403 456 630 655 0.037 8 52 13

 23

 258 311 4

3 621 742 772 0.037

 152 206 306 376 435 544 607 708 766 0.037

 52 89 2

8 259 288 304 338 456

30 0.037 73 137 428 454 621 634 667 680 735 768 0.037 127 370 171 20

 796 302 402 412 76

 775 0.037 137 288 296 30

 314 388 415 653 735 778 0.037 29 152 206 299 357 435 544 630 7

 775 0.037 170 2

2 3

7 469 482 527 5

4 636 644 717 0.037 127 171 296 299 311 402 412 415 65

 7

0.037 8 37 52

4 201 338 480 547 686 674 0.037 34 135 137 278 37

 428 634 650 768 772 0.037 20

 211 302 306 408 490

45 6

 724 763 0.037 52 152 232 264 388 415 490 674 735 775 0.037 37

2 64 242 339 453 4

 634 7

 772 0.037 170 171 299 418 44

 585 594 653 736 76

0.037 89 137 311 428 454 634 667 680 768 78

0.037 34 135 205 278 421 428 621 634 6

0 768 0.037 152 201 206 242 288 357 388 392 655 775 0.037 152 209 296 308 314 357 402 544 7

6 775 0.037 8 52 64 89 258 259 288 338 453 742 0.037 9 84 242 278 304 367 421 547 772 77

0.037 208 2

 288 304 338 435 607 653 655 778 0.037 151 171 309 314 408 4

0 644 715 735 763 0.037 34 137 205 278 415 428 621 680 768 772 0.037 34 52 205 236 242 311 66

 735 745 772 0.037 59 277 450 490 636 645 675 708 745 77

0.038 34 37 84 89 25

 288 338 453 821 674 0.038 40 211 231 277 30

 314 402 403 45

 636 0.038 135 205 242 278 428 454 621 680 768 78

0.038 29 171 206 296 338 415 585 645 655 78

0.038 29 152 302 388 392 453 454 544 6

 703 0.038

 2

 152 30

 402 450 456 544

08

45 0.038 34 135 278 311 428 621 680 742 768 772 0.038 9 64

9 201 242 304 621 687 674 778 0.038 9 34 37 137 201 242 28

 653 738 772 0.038 9 135 236 242 258 278 304 621 742 772 0.038 9 52 64 242 278 547 634 735 7

8 772 0.038 127 288 296 357 393 415 435 655 786 775 0.038

 52 64 278 367 547 634 653 735 772 0.038 8 37 52

4 201 23

 258 745 772 778 0.038 152 201 402 415 498 653 674 735 745 76

0.038 59 242 311 428 454 6

7 680 742 7

8 789 0.038 9 259 288 357 388 456 630 674 735 778 0.038 52 127 201 435 544 607 630 735 7

 778 0.038 9

4 1

 278 311 428 680 742 788 789 0.038 37 52 137 201 205 236 454 735 745 772 0.038 152 171 20

 299 357 388 415 435 655 682 0.038 127 174 206 288 304 392 435 630 655 708 0.038 8 52 89 309 376 398 392 435 453 745 0.038 8 52 64 258 302 338 453 621 6

 674 0.038 8 2

 64 236 258 25

 338 454 6

 763 0.038 37 52 64 201 236 242 258 304 742 772 0.038 34 73 135 137 27

 421 428 763 768 772 0.038 2

 152 20

 2

8 3

7 392 435 594 621 76

0.038 127 171 208 296 415 435 544

5 766 775 0.038 73 171 206 277 298 314 544 558 65

 775 0.038 9 170 408 421 527 542 544 644

45 775 0.038 8 37 64 206 258 259 338 454 630 753 0.038 137 278 311 428 454

21 634 658 742 7

8 0.038 8 9 64 135 201 338 435 630 748 77

0.038 127 302 435 409 544 547 644 645 724 775 0.038 171 296 314 412 544 644 6

8 6

5 735 76

0.038 15 152 211 231 232 305 415 708 724 766 0.038 171 28

 357 408 4

0 544 645 653 724 776 0.038 37 52 64 201 205 236 242 454 735 772 0.038 34 73 137 205 278 428 634 680 768 789 0.038 52 64 205 236 258 387 376 621 674 772 0.038

 137 205 259 30

 4

4 621 63

 

80 735 0.038 137 205 278 378 415 428 621 634 6

0 768 0.038 89 137 152 20

 236 258

 288 309 435 453 0.038 170 171 412 415 453 4

2 594 6

 682 76

0.039 8 9 52

9 258 288 304 338 38

 630 0.039 37 64 238 258 3

 454 621 63

 6

 674 0.039 206 277 357 402 408 435 449 490 558 644 0.039 9

9 135 152 205 259 304 376 630 742 0.039

 37 52 84 258 311 314 338 454 6

0.039

 52 89 126 258 28

 30

 338 454 630 0.039 15 206 302 306 402 412 636 645 653 735 0.039 15 89 137 152 288 296 357 3

8 415 674 0.039 15 40 127 171 206 408 415 544 594 708 0.039

 201 288 331 3

7 392 547 674 7

 778 0.039 41 89 205 415 421 428 680 742 768 789 0.039 37 52 64 23

 258 304 348 421 742 772 0.039 37

4 89 205 258 338 3

7 376 630 674 0.039 64 137 205 236 304 621 667 674 772 778 0.039 15 152 607 60

 644 65

 682 735 745 787 0.039 8 37 135 304 338 630 674 735 76

 778 0.039 13

 137 242 428 454 621 634 687 880 768 0.039 88 127 171 29

 29

 357 388 490 655 666 0.039 2

 52 288 2

 314 3

8 3

2 402 874 735 0.039 52 152 205 20

 288 304 338 348 388

55 0.039 29 59 152 20

 25

 2

8 357 357 388 655 674 0.039 41 73

3

0 123 2

 2

4 376 742 789 0.039 37 52 127 259 288 314 338 6

8 735 76

0.039 137 205 278 311 42

 454 634 680 768 7

0.039 9 258 259 2

 338 415 5

4 630 735 77

0.039 8

 2

8 304 335 388 392 547

55 674 778 0.039

7 137 205 311 37

 428 454 680 743 768 0.039 37 137 201 205 23

 34

 454

68 7

8 772 0.039

 37 52 64 201 242 27

 304 772 77

0.039 89 152 288 33

 37

 3

8 392 435 65

 778 0.039 8

 135 205 278 428 621 634 680 742 768 0.039 15 170 171 302 402 449 45

 594 682 766 0.039 2

 52 221 259 28

 3

7 388 630 6

 674 0.039 8 15 29 89 152 171 29

 299 7

 775 0.039 8 9 37 201 205 547 63

 6

 674 735 0.039 137 242 428 454 4

 621

34 6

7

80 742 0.039

 35 135 242 278 428 621 680 7

8 772 0.039 8 52 152 288 304 306 357 388 453 490 0.039 201 236 258 259 28

 482 547 674 735 778 0.039 170 171 232 296 29

 456 585 708 724 76

0.039 127 137 2

8 296 302 388 392 402 435 655 0.039 152 201 206 258 2

8 482 547 630 655 686 0.039 8 126 302 402 453 544 630 653 766 77

0.039

4 201 258 278 338 415 453 607 630 634 0.039 16 29 73 152 201 20

 288 299 724 76

0.039 64 8

 236 258 278 304 653 742 772 778 0.039 8 9 304 357 435 544 653

 742 778 0.039 89 135 137 242 428 454 680 742 768 778 0.039 89 135 205 25

 428 454 680 742 768 778 0.039 152 20

 25

 258 306 309 314 357 435 607 0.039 127 171 20

 252 408 415 450 544 644 76

0.039 15 302 3

3 408 412 450 636 653 682 708 0.039 89 135 201 25

 338 482 607

0 735 775 0.039 8 9 137 104 376 388 392 435 544 778 0.039 37 52 135 201 236 242 258 454 621 772 0.039 127 170 171 206 302 30

 412 724 745 76

0.040 8 9 8

 135 242 278 367 821 674 772 0.040 9 34 137 205 37

 428 634 667 680 768 0.040 8 89 137 152 288 338 357 415

74 778 0.040 34 137 205 278 428 680 763 768 772 7

0.040 34 137 205 278 375 428 621 680 765 7

0.040 8 64 258 401 454 634 666 667 674 787 0.040 8 37

9 151 205 206 258 304

 874 0.040 137 205 278 428 454 621 634 680 7

8 789 0.040 2

2 3

7 527 574 585 619 675 70

 775 787 0.040 97 137 311 428 454 634 667 680 742 7

8 0.040 38 213 367 40

 527 558 619 628 682 787 0.040 37

2 64 20

 236 242 2

9 367 735 772 0.040 206 259 277 296 306 402 412 645

55 724 0.040 206 211 262 2

 412 630 644 674 708 76

0.040 8 37 52

4 236 242 258 3

8 421 772 0.040 38 151 20

 302 3

7 392 408 703 715 7

3 0.040 15 29 127 388 544 547 594 630 655 724 0.040 8

 206 259 288 309 357 37

 435

 6

0.040 34 37 201 236 242 278 311 735 772 778 0.040 127 171 20

 304 306 482 544 653 686 7&6 0.040 52 64 201 236 242 304 421 621 674 772 0.040 304 30

 393 406 435 608 645 703 708 724 0.040 37 64 201 205 242 259 311 454 742 772 0.040 137 205 278 37

 428 498 821 634 680 788 0.040 127 231 314 357 402 544 644 682 7

 77

0.040 15 127 232 302 306 311 402 682 724 7

0.040 8 29 288 304 38

 392 435 630 655 778 0.040 2

 298 30

 314 388 402 415 435 544 653 0.040 8 127 171 2

 309 490 544 655 708 775 0.040 9 34 137 278 378 428 621 6

0 7

8 78

0.040 151 174 232 3

7 408 54

 644 682 715 763 0.040 127 20

 302 402 412 415 435 653

5 78

0.040 8 52 89 258 288 304 338 357 630 674 0.040 89 171 2

8 338 357 376 392 449 453 655 0.040 37 64 236 28

 338 454 4

0 66

 670 674 0.040 221 259 288 308 388 402 435 450 655 735 0.040 11 41 83 90 123 135 294 415 454

34 0.029 Columns Feature ID: feature index (see Table S10 for feature details) MAE: mean absolute error between observed and calculated ctDNA fractions from 652 samples

indicates data missing or illegible when filed

TABLE S17 Information on predictive pan-cancer features ID Transcript Gene Chr Site Region Group FPKM_(blood) 8 ENST00000221954.6 CEACAM4 19 42133442 promoter blood 32.81 9 ENST00000225275.3 MPO 17 56358296 promoter blood 7.23 11 ENST00000234347.9 PRTN3 19 840960 promoter blood 13.78 15 ENST00000262407.5 ITGA2B 17 42466873 promoter blood 12.34 29 ENST00000299663.7 CLEC4E 12 8693559 promoter blood 29.27 34 ENST00000307395.4 GP9 3 128779610 promoter blood 9.72 37 ENST00000312156.8 NFE2 12 54689544 promoter blood 11.15 38 ENST00000314412.6 FUT7 9 139927462 promoter blood 16.90 39 ENST00000314446.9 LILRB2 19 54785039 promoter blood 7.87 40 ENST00000318507.6 CXCR2 2 218990727 promoter blood 157.27 41 ENST00000324134.10 NLRP12 19 54327597 promoter blood 9.17 52 ENST00000342063.4 C19orf35 19 2282175 promoter blood 8.64 64 ENST00000375448.4 PADI4 1 17634692 promoter blood 95.04 73 ENST00000380299.3 HBD 11 5255878 promoter blood 138.84 83 ENST00000392841.1 HMBS 11 118958697 promoter blood 7.28 89 ENST00000398421.6 NCF1 7 74188358 promoter blood 11.04 90 ENST00000398632.3 MX2 21 42774561 promoter blood 7.28 97 ENST00000413580.5 PHOSPHO1 17 47308128 promoter blood 42.76 123 ENST00000460208.1 LILRB3 19 54721567 promoter blood 51.15 126 ENST00000462275.5 TBXAS1 7 139529072 promoter blood 6.07 127 ENST00000462927.5 CYTH4 22 37678566 promoter blood 26.95 135 ENST00000465984.5 SLC11A1 2 219246911 promoter blood 10.54 137 ENST00000466151.1 PADI2 1 17409921 promoter blood 7.13 142 ENST00000467972.5 SLC12A9 7 100454416 promoter blood 6.80 151 ENST00000469799.5 SLC11A1 2 219247002 promoter blood 8.27 152 ENST00000469886.5 CYTH4 22 37678556 promoter blood 6.16 170 ENST00000478902.1 ZDHHC18 1 27177620 promoter blood 12.52 171 ENST00000479534.5 PADI2 1 17401846 promoter blood 5.78 174 ENST00000480825.6 CSF3R 1 36941928 promoter blood 127.36 201 ENST00000487761.5 GPSM3 6 32160645 promoter blood 14.37 205 ENST00000488970.1 BTK X 100609209 promoter blood 7.40 206 ENST00000489175.1 KCNE1 21 35884505 promoter blood 6.75 211 ENST00000490872.1 SLC11A1 2 219254688 promoter blood 26.15 213 ENST00000492413.5 SLC11A1 2 219247010 promoter blood 17.89 221 ENST00000495406.1 CDK5RAP2 9 123152555 promoter blood 10.53 231 ENST00000500323.2 DOK3 5 176935878 promoter blood 10.88 232 ENST00000502380.1 DOK3 5 176937383 promoter blood 8.44 236 ENST00000509314.5 FBXL5 4 15661487 promoter blood 10.24 242 ENST00000517813.1 DENND3 8 142194587 promoter blood 13.47 258 ENST00000523369.1 LCP2 5 169685502 promoter blood 9.88 259 ENST00000523530.1 DENND3 8 142201373 promoter blood 7.23 262 ENST00000526387.5 TBC1D10C 11 67171386 promoter blood 7.10 264 ENST00000526980.5 CSF3R 1 36948500 promoter blood 184.80 277 ENST00000532897.5 MKNK1 1 47037972 promoter blood 6.23 278 ENST00000533815.2 BTNL8 5 180336564 promoter blood 5.72 279 ENST00000533968.1 SPI1 11 47400038 promoter blood 12.90 288 ENST00000539932.5 SLC11A1 2 219246926 promoter blood 50.32 294 ENST00000542481.1 ATG16L2 11 72534940 promoter blood 25.18 296 ENST00000543576.5 DENND1C 19 6481798 promoter blood 12.06 299 ENST00000546200.5 ARHGAP9 12 57871634 promoter blood 66.03 302 ENST00000551000.1 ARHGAP9 12 57871650 promoter blood 8.28 304 ENST00000553070.5 NFE2 12 54694799 promoter blood 23.61 306 ENST00000554736.5 GNG2 14 52328042 promoter blood 9.30 309 ENST00000558332.3 IL16 15 81591757 promoter blood 7.66 311 ENST00000559341.5 MAN2A2 15 91459225 promoter blood 8.61 314 ENST00000560377.5 PSTPIP1 15 77287726 promoter blood 8.38 331 ENST00000566082.1 USB1 16 58049017 promoter blood 6.82 338 ENST00000570439.1 ACAP1 17 7248650 promoter blood 5.27 348 ENST00000574548.1 RNF167 17 4847675 promoter blood 6.40 357 ENST00000581974.1 DHRS13 17 27226541 promoter blood 5.97 367 ENST00000587287.1 RASGRP4 19 38902036 promoter blood 6.80 376 ENST00000590974.1 LYL1 19 13213975 promoter blood 5.48 388 ENST00000597611.7 FKBP8 19 18654887 promoter blood 9.25 392 ENST00000598529.5 MYO1F 19 8619448 promoter blood 16.08 393 ENST00000598907.5 SHKBP1 19 41084102 promoter blood 14.71 402 ENST00000601502.1 MYO1F 19 8610602 promoter blood 8.05 403 ENST00000602101.6 RASAL3 19 15575325 promoter blood 7.16 408 ENST00000605039.5 BIN2 12 51717938 promoter blood 11.02 412 ENST00000612844.4 FOLR3 11 71846756 promoter blood 13.11 415 ENST00000615340.4 RASGRP4 19 38916837 promoter blood 6.88 416 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 421 ENST00000008938.4 PGLYRP1 19 46525993 junction blood 148.76 428 ENST00000221954.6 CEACAM4 19 42133268 junction blood 32.81 429 ENST00000225275.3 MPO 17 56357966 junction blood 7.23 435 ENST00000262407.5 ITGA2B 17 42466654 junction blood 12.34 449 ENST00000299663.7 CLEC4E 12 8693357 junction blood 29.27 450 ENST00000299665.2 CLEC4D 12 8666356 junction blood 10.47 452 ENST00000304076.6 VAV1 19 6773022 junction blood 7.61 453 ENST00000304361.8 CLEC12A 12 10124286 junction blood 10.23 454 ENST00000307395.4 GP9 3 128779693 junction blood 9.72 456 ENST00000310544.8 PHOSPHO1 17 47307830 junction blood 30.92 469 ENST00000338372.6 VSTM1 19 54566998 junction blood 10.71 482 ENST00000375448.4 PADI4 1 17634809 junction blood 95.04 490 ENST00000380299.3 HBD 11 5255572 junction blood 138.84 498 ENST00000392841.1 HMBS 11 118958788 junction blood 7.28 527 ENST00000448367.5 FES 15 91432866 junction blood 6.30 542 ENST00000464994.5 IL1R2 2 102608495 junction blood 12.24 544 ENST00000465984.5 SLC11A1 2 219247098 junction blood 10.54 546 ENST00000466151.1 PADI2 1 17409731 junction blood 7.13 547 ENST00000466612.5 ABTB1 3 127392451 junction blood 6.18 558 ENST00000469532.1 RAC2 22 37640154 junction blood 9.83 561 ENST00000471836.1 PARVG 22 44577797 junction blood 6.53 574 ENST00000478902.1 ZDHHC18 1 27177722 junction blood 12.52 585 ENST00000483665.6 FCGR2A 1 161475342 junction blood 6.60 594 ENST00000485991.5 CFP X 47489168 junction blood 5.10 607 ENST00000488970.1 BTK X 100608858 junction blood 7.40 608 ENST00000489175.1 KCNE1 21 35884325 junction blood 6.75 619 ENST00000495406.1 CDK5RAP2 9 123152019 junction blood 10.53 621 ENST00000496915.1 PREX1 20 47258945 junction blood 5.23 628 ENST00000504910.1 HK3 5 176318389 junction blood 6.36 630 ENST00000509314.5 FBXL5 4 15661350 junction blood 10.24 634 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 636 ENST00000517813.1 DENND3 8 142195377 junction blood 13.47 644 ENST00000520887.1 FAM49B 8 130859050 junction blood 7.15 645 ENST00000521442.1 ATP6V1B2 8 20075793 junction blood 8.33 653 ENST00000526387.5 TBC1D10C 11 67171411 junction blood 7.10 655 ENST00000527031.5 JAK3 19 17958755 junction blood 6.17 666 ENST00000532897.5 MKNK1 1 47037735 junction blood 6.23 667 ENST00000533815.2 BTNL8 5 180336697 junction blood 5.72 670 ENST00000534754.5 SORL1 11 121483541 junction blood 9.84 674 ENST00000538842.1 ATG16L2 11 72527872 junction blood 6.35 675 ENST00000539134.1 RELT 11 73104962 junction blood 6.58 680 ENST00000542481.1 ATG16L2 11 72535167 junction blood 25.18 682 ENST00000543576.5 DENND1C 19 6481690 junction blood 12.06 703 ENST00000564072.1 SLCO3A1 15 92706776 junction blood 8.74 708 ENST00000564894.1 RNF166 16 88767670 junction blood 7.90 715 ENST00000567038.1 XPO6 16 28113168 junction blood 8.97 717 ENST00000568760.5 DEF8 16 90024068 junction blood 7.24 724 ENST00000571303.1 MLKL 16 74725175 junction blood 5.93 735 ENST00000581287.5 SLC16A3 17 80194107 junction blood 11.97 736 ENST00000581974.1 DHRS13 17 27226145 junction blood 5.97 742 ENST00000585852.5 FMNL1 17 43308054 junction blood 19.81 745 ENST00000587265.1 CA4 17 58235488 junction blood 5.45 763 ENST00000595725.5 CD37 19 49838866 junction blood 20.04 766 ENST00000597611.7 FKBP8 19 18654719 junction blood 9.25 768 ENST00000598201.5 SHKBP1 19 41086391 junction blood 12.36 772 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 775 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 776 ENST00000600463.1 IFI30 19 18286032 junction blood 6.41 778 ENST00000601502.1 MYO1F 19 8610534 junction blood 8.05 787 ENST00000614135.4 RASGRP4 19 38916709 junction blood 8.18 789 ENST00000616356.4 FCN1 9 137809615 junction blood 16.99 666 ENST00000532897.5 MKNK1 1 47037735 junction blood 6.23 667 ENST00000533815.2 BTNL8 5 180336697 junction blood 5.72 674 ENST00000538842.1 ATG16L2 11 72527872 junction blood 6.35 680 ENST00000542481.1 ATG16L2 11 72535167 junction blood 25.18 695 ENST00000559341.5 MAN2A2 15 91459486 junction blood 8.61 708 ENST00000564894.1 RNF166 16 88767670 junction blood 7.9 736 ENST00000581974.1 DHRS13 17 27226145 junction blood 5.97 742 ENST00000585852.5 FMNL1 17 43308054 junction blood 19.81 766 ENST00000597611.7 FKBP8 19 18654719 junction blood 9.25 772 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 775 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 776 ENST00000600463.1 IFI30 19 18286032 junction blood 6.41 787 ENST00000614135.4 RASGRP4 19 38916709 junction blood 8.18 789 ENST00000616356.4 FCN1 9 137809615 junction blood 16.99 Columns ID: feature index Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood. Their FPKM values in tumors of 20 cancer types are all <1.

TABLE S18 All predictive feature combinations for CRC using in silico samples generated with random subsets of healthy samples. Feature ID MAE 364 379 475 788 730 905 0.030 284 384 475 788 790 906 0.031 284 364 379 475 758 905 0.031 284 364 379 475 790 906 0.032 179 407 788 830 900 905 0.032 364 379 760 790 852 903 0.033 39 540 760 788 830 900 0.033 35 39 410 540 760 830 0.033 284 364 475 760 788 905 0.033 364 540 760 830 903 905 0.033 364 379 475 703 788 905 0.033 284 364 475 703 788 905 0.033 364 475 760 788 790 905 0.034 35 476 673 830 852 890 0.034 364 379 540 760 790 903 0.034 364 379 475 703 760 790 0.034 364 379 407 760 790 903 0.034 39 125 379 478 852 903 0.034 39 364 475 788 790 905 0.034 364 379 475 788 900 905 0.034 39 379 410 540 703 760 0.034 39 379 407 540 760 790 0.034 364 475 540 788 790 905 0.034 364 760 790 830 900 903 0.035 410 478 540 688 760 830 0.035 478 760 788 830 900 903 0.035 379 407 475 788 790 905 0.035 364 475 703 788 790 905 0.035 39 364 475 703 788 905 0.035 364 475 788 790 900 905 0.035 35 39 301 540 830 903 0.035 379 475 540 788 790 905 0.035 379 475 703 788 790 905 0.035 364 379 760 790 900 903 0.035 115 126 480 529 830 903 0.035 284 410 469 540 571 830 0.035 39 379 407 703 790 903 0.035 384 379 540 703 793 903 0.035 36 322 469 478 830 903 0.035 284 364 475 703 790 905 0.036 364 407 475 788 790 905 0.036 126 284 410 480 830 890 0.036 39 364 379 407 540 903 0.036 39 115 379 407 790 903 0.036 364 379 478 790 900 903 0.037 39 67 379 703 900 903 0.037 39 379 407 540 703 903 0.037 407 478 760 788 830 900 0.037 39 115 379 407 703 790 0.037 39 115 284 379 540 703 0.037 86 284 478 760 830 903 0.037 364 475 540 788 900 905 0.037 407 760 788 830 900 903 0.037 39 379 407 703 760 903 0.037 86 364 379 410 900 903 0.037 301 470 473 553 639 890 0.037 364 475 760 788 900 905 0.037 35 39 478 540 673 830 0.037 379 407 475 703 790 905 0.037 39 284 379 703 760 903 0.037 126 364 379 407 475 760 0.037 39 126 478 830 852 903 0.038 364 379 407 410 760 903 0.038 126 284 410 469 540 830 0.038 284 359 410 469 540 830 0.038 364 475 703 788 900 905 0.038 256 478 594 727 830 852 0.038 364 407 475 703 788 905 0.038 39 126 379 410 469 478 0.038 379 407 475 703 786 905 0.038 364 407 475 703 790 905 0.038 86 407 410 760 830 900 0.038 39 364 703 830 900 903 0.038 379 475 703 788 790 900 0.038 39 284 540 594 727 830 0.038 35 284 410 571 760 830 0.038 703 760 790 830 900 903 0.038 86 470 655 842 856 890 0.038 35 284 410 540 571 830 0.038 39 475 703 786 790 905 0.038 284 379 407 410 469 571 0.038 379 540 760 790 900 903 0.038 379 407 760 790 900 903 0.038 86 115 126 469 553 721 0.039 284 322 410 469 540 830 0.039 35 39 410 478 540 830 0.039 284 469 478 540 571 830 0.039 407 760 790 830 900 903 0.039 284 410 480 540 571 830 0.039 35 86 284 469 478 830 0.039 284 410 469 529 540 830 0.039 115 284 379 407 760 790 0.039 39 268 306 322 466 744 0.039 284 410 478 540 571 830 0.039 35 86 306 673 793 852 0.039 407 703 760 790 830 903 0.039 115 364 379 407 760 903 0.039 284 410 480 629 760 830 0.039 284 478 540 571 830 852 0.039 72 197 256 395 473 858 0.039 364 478 760 830 900 903 0.039 284 379 410 673 760 852 0.039 39 284 379 407 703 903 0.039 39 379 407 410 760 900 0.039 364 540 760 830 900 903 0.040 39 407 475 703 788 905 0.040 35 364 379 540 703 903 0.040 72 204 301 451 473 639 0.040 18 70 256 439 467 777 0.040 86 359 391 395 455 890 0.040 35 478 540 673 760 830 0.040 364 379 407 478 540 903 0.040 67 364 379 407 760 903 0.040 39 379 407 703 900 903 0.040 18 72 275 393 468 842 0.040 284 478 540 727 830 690 0.040 35 39 703 793 852 903 0.040 468 469 553 559 652 842 0.040 407 540 760 790 830 900 0.040 Columns Feature ID: feature index (see Table S3 for feature details) MAE: mean absolute error between observed and calculated ctDNA fractions from 344 samples

TABLE S19 Information on predictive features for CRC using in silico samples generated with random subsets of healthy samples. ID Transcript Gene Chr Site Region Group FPKM_(blood) FPKM_(tumor) 18 ENST00000245451.8 BMP4 14 54423529 promoter tumor 0 16.43 35 ENST00000267101.7 ERBB3 12 56473645 promoter tumor 0 40.98 39 ENST00000270560.3 TM4SF5 17 4675187 promoter tumor 0 18.39 67 ENST00000310836.10 UGT8 4 115519611 promoter tumor 0.04 14.08 70 ENST00000311620.6 ANKS4B 16 21244986 promoter tumor 0 10.61 72 ENST00000317508.10 PRSS8 16 31147083 promoter tumor 0.11 143.22 86 ENST00000332149.9 TMPRSS2 21 42880086 promoter tumor 0.02 43.57 115 ENST00000361084.9 RAB25 1 156030951 promoter tumor 0.07 131.5 126 ENST00000368554.8 PRAP1 10 135122914 promoter tumor 0 32.41 179 ENST00000425042.6 HID1 17 72968829 promoter tumor 0.23 13.99 197 ENST00000463201.2 PRAP1 10 135164879 promoter tumor 0 54.46 204 ENST00000478194.1 FERMT1 20 6074819 promoter tumor 0 27 256 ENST00000588605.5 C19orf33 19 38794804 promoter tumor 0.22 18.46 268 ENST00000605618.5 LSR 19 35739922 promoter tumor 0.22 31.85 275 ENST00000619895.4 TMC4 19 54676865 promoter tumor 0.35 33.05 284 ENST00000234347.9 PRTN3 19 840960 promoter blood 13.78 0 301 ENST00000299663.7 CLEC4E 12 8693559 promoter blood 29.27 0.2 306 ENST00000310544.8 PHOSPHO1 17 47307890 promoter blood 30.92 0.08 322 ENST00000355524.7 FCAR 19 55385736 promoter blood 53.04 0.07 359 ENST00000398421.6 NCF1 7 74188358 promoter blood 11.04 0.04 364 ENST00000413580.5 PHOSPHO1 17 47308128 promoter blood 42.76 0.05 379 ENST00000454703.6 ACSL1 4 185747273 promoter blood 35.07 0.78 391 ENST00000480395.5 TRIM22 11 5717722 promoter blood 17.36 0.7 393 ENST00000483750.5 WAS X 48542217 promoter blood 34.49 0.17 395 ENST00000485743.1 HBB 11 5248302 promoter blood 128.52 0 407 ENST00000496823.1 BCL6 3 187463247 promoter blood 21.33 0.2 410 ENST00000509314.5 FBXL5 4 15661487 promoter blood 10.24 0 439 ENST00000553070.5 NFE2 12 54694799 promoter blood 23.61 0 451 ENST00000585901.6 TYROBP 19 36399149 promoter blood 13.4 0.19 455 ENST00000588673.3 OAZ1 19 2270290 promoter blood 24.28 0.69 466 ENST00000596764.5 VAV1 19 6772739 promoter blood 12.25 0.59 467 ENST00000597852.5 CD37 19 49838675 promoter blood 13.98 0.2 468 ENST00000598034.5 GMFG 19 39826646 promoter blood 43.77 0.45 469 ENST00000599180.2 FFAR2 19 35939203 promoter blood 24.79 0 470 ENST00000599716.5 SHKBP1 19 41082793 promoter blood 10.66 0.22 473 ENST00000602185.5 GMFG 19 39826645 promoter blood 14.09 0 475 ENST00000605039.5 BIN2 12 51717938 promoter blood 11.02 0.11 478 ENST00000615439.4 RASGRP4 19 38916945 promoter blood 10.11 0 480 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 0.07 529 ENST00000291525.11 TFF3 21 43735403 junction tumor 0 209.02 540 ENST00000300119.7 MYO1A 12 57443671 junction tumor 0 15.11 553 ENST00000311620.6 ANKS4B 16 21245222 junction tumor 0 10.61 559 ENST00000318683.6 B3GNT3 19 17906015 junction tumor 0 57.75 571 ENST00000334869.8 LGMN 14 93214834 junction tumor 0.94 45.73 594 ENST00000360779.3 SDCBP2 20 1309729 junction tumor 0 17.84 639 ENST00000394201.8 SCOC 4 141294871 junction tumor 0.53 14.61 652 ENST00000419308.6 FOXA2 20 22564830 junction tumor 0 13.51 655 ENST00000425042.6 HID1 17 72968686 junction tumor 0.23 13.99 673 ENST00000472782.1 ATP5G3 2 176046384 junction tumor 0.62 10.87 688 ENST00000514985.5 SEPP1 5 42811938 junction tumor 0.59 49.95 703 ENST00000543623.5 PLCD3 17 43192462 junction tumor 0.27 14.58 721 ENST00000588605.5 C19orf33 19 38794923 junction tumor 0.22 18.46 727 ENST00000597153.5 LGALS4 19 39303482 junction tumor 0 20.51 744 ENST00000234347.9 PRTN3 19 841069 junction blood 13.78 0 760 ENST00000297239.10 SYTL3 6 159082417 junction blood 10.79 0.54 777 ENST00000343534.9 C1orf162 1 112016652 junction blood 37.68 0.74 788 ENST00000367025.7 TRAF3IP3 1 209929654 junction blood 17.52 0.64 790 ENST00000367535.7 NCF2 1 183559291 junction blood 75.23 0.98 793 ENST00000368015.1 ARHGAP30 1 161039410 junction blood 20.61 0.58 830 ENST00000454703.6 ACSL1 4 185747070 junction blood 35.07 0.78 842 ENST00000485743.1 HBB 11 5248160 junction blood 128.52 0 852 ENST00000496823.1 BCL6 3 187463198 junction blood 21.33 0.2 856 ENST00000509339.1 MXD3 5 176734782 junction blood 30.07 0.08 858 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 0.1 890 ENST00000589900.5 ICAM3 19 10450215 junction blood 21.24 0 900 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 0.22 903 ENST00000605039.5 BIN2 12 51717806 junction blood 11.02 0.11 905 ENST00000615439.4 RASGRP4 19 38916709 junction blood 10.11 0 Columns ID: feature index, same as Table S3 Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood FPKM_(tumor): FPKM value in tumor of colorectal cancer

TABLE S20 Columns Feature ID: feature index (see Table S10 for feature details) MAE: mean absolute error between observed and calculated ctDNA fractions from 652 samples All predictive pan-cancer feature combinations using in silico samples generated with random subsets of healthy samples. Feature ID MAE Feature ID MAE 34 41 90 126 294 376 388 415 742 772 0.034 29 201435 454667 630 742 766 772 787 0.041 34 41 90 126 294 376 388 415 500 772 0.034 34 41 288 490667 680 742 768 772 787 0.041 34 41 90 126 236 294 376 388 415 500 0.036 29 34 36 64 436 667 680 742 766 772 0.041 34 41 90 126 201 294 376 388 415 500 0.036 29 128 428 454 634 645 680 742 772 787 0.041 34 41 90 126 201 294 376 388 415 772 0.036 34 41 90 126 236 294 376 388 742 772 0.041 34 4 1 64 90 126 294 388 415 490 500 0.036 57 90 126 201 236 294 388 415 490 500 0.041 34 41 64 90 126 294 376 388 415 500 0.036 41 90126 201 236 294 376 388 456 500 0.041 34 41 90 1 26 201 294 388 500 742 772 0.037 34 4190126135 201 294 388 500 772 0.041 29 34 415 428 490 645 680 742 766 772 0.038 34 135 415 645667 680 742 766 772 775 0.041 34 41 90 126 201 230 294 376 388 500 0.038 34 41 90126135 201 294 388 490 500 0.041 29 34 36 64 428 490 742 766 772 775 0.038 29 36 396 415 428 435 454 742 766 789 0.041 34 41 64 90 126 201 294 388 742 772 0.038 29 135 428 454 667 680 766 772 775 789 0.042 41 90 126 201 236 294 376 388 415 500 0.038 34 41 64 90 126 135 201294 388 500 0.042 29 57 64 126 428 454 742 766 772 789 0.038 34 41 64 90 126 201 294 376 388 772 0.042 34 41 90 126 201 236 294 388 490 500 0.039 34 41 90 126 236 294 376 388 500 772 0.042 34 126 135 428 680 742 766 772 787 789 0.039 41 84 90126 201 236 294 378 388 500 0.042 34 41 90 126 201 294 388 500 772 775 0.039 13 29 396 415 428 435454 880 786 789 0.042 34 41 90 1 26 201 236 294 376 388 772 0.039 29 34 135 311 428 680 742 766 772 775 0.042 29 34 80135 415 428 742 766 772 775 0.039 41 90 126 201 236 294 378 388 490 500 0.042 34 41 90 201 236 294 376 388 500 772 0.033 64 90 126135 201 294 376 388 415 500 0.042 41 64 30 1 26 294 376 388 415 490 500 0.039 41 90 126 135 201 236 294 376 388 500 0.042 41 64 90 1 26 201 294 376 388 415 500 0.039 29135142 201 242 454 742 766 772 775 0.042 41 90 126 135 236 294 376 388 415 500 0.039 34 64 201 242 428 680 742 766 772 787 0.042 34 41 90 135 201 236 294 376 388 500 0.039 34 36 41 135 311 667 680 742772 775 0.042 34 41 64 90 126 201 294 376 415 500 0.039 123 135 396 415 435 454 500 630 742 766 0.042 41 64 SO 201 236 294 376 388 415 500 0.039 29 138 242 428 454 742 766 772 776 789 0.042 34 41 90126 201 294 376 388 500 772 0.040 288 402 490 547 634 645 667 680 742 787 0.042 34 41 64 90 201 236 294 376 388 500 0.040 29 34 135 428 667 680 742 766 772 775 0.042 41 57 90 126 201 236 294 376 388 500 0.040 34 41 00 126 294 376 388 503 742 772 0.042 34 41 90 126 201 294 376 388 490 500 0.049 135 201 402 428 435 454 742 766 775 789 0.043 123 402 415 456490 645 867 880 742 788 0.040 34 41 64 90 126 234 376 388 490 772 0.043 34 41 242 415 667 680 742 788 772 789 0.040 34 41 90 1 26 294 378 388 490 500 772 0.043 29 34 135 435 667 680 742 766 772 787 0.040 29 135 396 402 428 435 454 490 766 775 0.043 34 41 64 90 201 234 378 415 500 775 0.040 29126 135 388 415 428 435 454 490 789 0.043 34 41 80 126 135 201 294 376 388 500 0.040 135 201 402 428 454 630 742 766 772 787 0.043 34 41 80 1 42 311 415 742 766 772 775 0.040 29 242 428 454 645 867 680 766 775 789 0.043 41 57 64 90 126 201 294 376 396 500 0.040 29 201 428 454 667 680 742 756 772 789 0.043 29 34 123 136 428 680 742 765 772 787 0.040 34 41 90 126 135 201 294 376 490 500 0.043 126 396415428454667 880 742 766 789 0.040 34 36 41 242 288 311 742 766 772 775 0.043 34 41 64 90 126 201 294 378 388 500 0.040 29 201428 435 454 667 680 742 786 789 0.043 34 41 64 90 126 201 294 388 SOO 772 0.041 57 64 90 1 26 201 294 376 388 490 500 0.043 57 90 126 201 294 376 388 415 456 500 0.041 8 19 296 338 415 466 680 766 775 789 0.043 34 36 126 428 645 680 742 768 772 775 0.041 29 135 201428 435 454 742 758 775 789 0.043 34 41 64 90 126 201 294 388 490 500 0.041 34 41 64 90 126 135 201 294 376 506 0.043 29 135 415 428 454 680 742 786 772 789 0.041 29135142 454 667 680 742 766 772 775 0.043 34 41 57 90 126 294 388 500 742 772 0.041 34 36 41 80 135 242 766 772 775 787 0.043 123 135142 242 296 402 456 657 680 787 0.041 29 123 236 428 454 742 766 772 775 789 0.043 Feature ID MAE Feature © MAE 34 41 64 90126 294 376 338 500 772 0-043 34 135 402 630 634 645660 742 766 772 0.046 142 288 396 402 435 454 634 645666 775 0.043 135 201 428 435 454 674 860 742 766 789 0.046 34 41 64 90 1 26 294 388 500 742 772 0.044 8123 288 402 490 667 680 742 766 775 0.046 19126 135 386 396 428 454 667 680 769 0.044 123 201 3S6 402 428 435 454 766 775 789 0.046 135 242 396 402 415 634 645 667 674 680 0.044 205 258 338 402 456 490 736 788 787 789 0.046 126 1 35 423 454 645667 680 766 772 789 0.044 29 396 402 428 435 456 634 667 680 787 0.046 41 84 90 126 135 201294 376 388 500 0.044 123 435454 630 634 645 667 680 787 789 0.046 34 41 90 126 201 294 376 456 500 772 0.044 19 288 331 396 402 415 435 630 634 742 0.046 34 41 90 126 135 294 388 490 500 772 0.044 396 428 435 454 667 680 742 766 775 789 0.046 201 415 454 634 645 667 680 742 766 772 0.044 36 201 428 435 454 490 500 680 766 789 0.046 29 34 84 428 667 680 742 768 772 789 0.044 64 123 135 142 205 278 634 645 674 787 0.047 135142 428 454 630 742 766 772 775 789 0.044 29135142 242 388 428 454 490 707 789 0.047 29135 454 490 667 680 742 766 772 775 0.044 237 288 296 331 338 435 547 634 775 787 0.047 29123135 376 396 454 680 742 766 789 0.044 34 41 135 634 645 667 680 742 766 772 0.047 135 242 378 396 402 415 428 435 454 490 0.044 123 142 242 288 415 634 645 667 680 789 0.047 34 41 90 201 294 376 500 645 742 772 0.044 135 396 402 634 645 667 674 680 787 789 0.047 64 90 126 135 201 236 294 376 388 500 0.044 8 19 64 142 288 296 435 667 674 787 0.047 37 278 288 331 338 376 547 634 645 787 0.044 118 225 236 258 278 286 296 311 456 589 0.047 34 41 57 90 201 294 376 500 742 772 0.044 19 64 415 490 634 645 674 775 776 789 0.047 10 29 36 135 142 388 396435 454 789 0.044 8 64 123135142 278 415 634 645 674 0.047 90126135 201 238 294 376 388 490 500 0.044 29123 201 428 435 454 490 500 766 775 0.047 29123 135 142 396 415 435 454 766 775 0.944 19 36 201 428 435 454 742 766 775 788 0 047 29 306 428 435 454 490 680 742 766 789 0.045 29123 454 645667 680 742 766 772 789 0.047 29 64 135142 428 454 490 766 772 789 0.045 36 135 142 201 415 454 500 766 775 789 0.047 29 428 435 454 634 645 680 742 766 772 0.045 8 19 142 278 396 415 674 766 775 789 0.047 135 396 402 435 454 480 742 766 775 789 0.045 123 288 435 634 645 680 742 766 772 775 0.048 29135 454 634 845 667 680 742 766 772 0.045 34 41 311 630 634 645 667 680 742 772 0.048 29135 428 454 645 667 680 742 766 772 0.045 8 64 278 286 296 338 544 634 645 787 0.048 34 41 64 90 126 294 376 388 490 500 0.045 8 64 205 278 415 544 634 645 674 789 0.048 29 142 288 428 454 667 680 742 766 772 0.045 123 135 242 547 634 645 667 680 742 776 0.048 123 205 288 402 435 634 645 667 680 787 0.045 8 37 142 278 288 296 331 338 415 634 0.048 34 36 135 428 490 687 680 742 766 772 0.045 34 3641 80135242 311435 490 787 0.048 29 428 454 634 645 667 680 742 766 772 0.045 29 34 36 57135 242 428 772 775 789 0.048 29 38 8 428 454 634 645 667 680 742 772 0.045 34 135 428 834 845 667 680 742 7S6 772 0.048 29135 396 428 454 490 742 766 775 789 0.045 142 278 288 396 454 630 634 645 666 789 0.048 41 64 90 1 35 201 294 376 388 456 500 0.045 288 296 402 547 630 634 645 667 674 680 0.046 29142 396 428 435 454 490 766 775 789 0.045 8 123 135 142 242 396 402 456 490 787 0.048 29 135 415 428 435 454 500 766 775 789 0.045 B 142 237 258 296 402 456 695 776 787 0.048 29135 428 454 490 680 742 766 772 789 0.045 123 242 288 428 634 645 667 680 766 775 0.048 19 135 142 415 428 454 490 766 775 789 0.045 142 278 288 396 428 454 634 645 775 789 0.049 64 205 225 278 296 416 544 634 645 674 0.045 83 205 225 236 286 402 456 544 589 708 0.049 29 135 142 428 454 667 680 742 768 772 0.045 123 242 288 396 402 034 045 607 680 742 0.049 29 34 288 428 435 667 680 742 766 772 0.045 142 205 278 288 396 415 435 634 645 742 0.049 123 278 288 396 415 435 454 456 766 789 0.045 8 288 296 415 456 634 645 667 680 766 0.049 29 388 428 435 454 645 667 680 742 772 0.045 36 225 288 428 500 667 674 680 787 789 0.049 8 142 415 435 645 667 674 680 766 775 0.045 135 376 402 415 428 435 454 5® 775 789 0.049 29135 428 454 490 634 645 680 766 772 0.045 29 123 135 396 454 667 674 680 787 789 0.049 64 90 126 201 236 294 376 388 490 500 0.045 8 123 242 288 296 415 742 766 775 789 0.049 64 90 125135 201 294 376 388 490 500 0.046 135 142 428 454 634 645 667 680 742 766 0.049 34 428 435 667 680 742 766 772 775 789 0.046 19 118 278 288 296 338 547 634 653 787 0.049 36135 428 435 454 645 667 680 742 766 0.046 19 64 123 142 288 396 415 674 742 769 0.049 Feature ID MAE 8 29118 135 142 205 242 415 674 680 0.049 64 135142 242 396 415 456 634 645 667 0.049 142 288 396 435 454 430 630 634 645 666 0.049 142 242 338 416 544 634 645 667 680 787 0.049 9 211 236 258 296 348 376 544 621 666 0.049 258 357 402 415 456 544 621 666 674 695 0.049 142 278 331 396 428435 454 634 645 787 0.049 29 123142 205 288 634 645 667 680 787 0.049 8 19 64 205 278 288 296 338 653 787 0.049 29 36 64 135 142 428 435454 775 787 0.049 123 142 237 236 396 415 645 667 680 776 0.049 286 288 296 490 547 634 645 666 667 787 0.049 19 29 123 135 376 396 634 645 680 766 0.050 123 142 205 396 435 454 456 680 742 766 0.050 236 242 258 306 402 544 621 666 674 695 0.050 29 225 288 296 461 634 645 667 674 680 0.050 19 135142 396 435 454 674 775 787 789 0.050 8 80123 205 237 288 396 402 766 775 0.050 118 205 547 634 645 667 674 680 695 787 0.050 8 52 64 278 288 296 338 415 435 490 0.050 15 225 306 311 402 469 589 607 630 695 0.050

TABLE S21 Information on predictive pan-cancer features using in silico samples generated with random subsets of healthy samples. ID Transcript Gene Chr Site Region Group FPKM_(blood) 8 ENST00000221954.6 CEACAM4 19 42133442 promoter blood 32.81 9 ENST00000225275.3 MPO 17 56358296 promoter blood 7.23 15 ENST00000262407.5 ITGA2B 17 42466873 promoter blood 12.34 19 ENST00000264260.6 IL18RAP 2 103035149 promoter blood 42.11 29 ENST00000299663.7 CLEC4E 12 8693559 promoter blood 29.27 34 ENST00000307395.4 GP9 3 128779610 promoter blood 9.72 36 ENST00000310544.8 PHOSPHO1 17 47307890 promoter blood 30.92 37 ENST00000312156.8 NFE2 12 54689544 promoter blood 11.15 41 ENST00000324134.10 NLRP12 19 54327597 promoter blood 9.17 52 ENST00000342063.4 C19orf35 19 2282175 promoter blood 8.64 57 ENST00000355524.7 FCAR 19 55385736 promoter blood 53.04 64 ENST00000375448.4 PADI4 1 17634692 promoter blood 95.04 80 ENST00000391726.7 FCAR 19 55385704 promoter blood 6 83 ENST00000392841.1 HMBS 11 118958697 promoter blood 7.28 90 ENST00000398632.3 MX2 21 42774561 promoter blood 7.28 118 ENST00000452208.1 RGL4 22 24038671 promoter blood 64.94 123 ENST00000460208.1 LILRB3 19 54721567 promoter blood 51.15 126 ENST00000462275.5 TBXAS1 7 139529072 promoter blood 6.07 135 ENST00000465984.5 SLC11A1 2 219246911 promoter blood 10.54 142 ENST00000467972.5 SLC12A9 7 100454416 promoter blood 6.8 201 ENST00000487761.5 GPSM3 6 32160645 promoter blood 14.37 205 ENST00000488970.1 BTK X 100609209 promoter blood 7.4 211 ENST00000490872.1 SLC11A1 2 219254688 promoter blood 26.15 225 ENST00000496915.1 PREX1 20 47259276 promoter blood 5.23 236 ENST00000509314.5 FBXL5 4 15661487 promoter blood 10.24 237 ENST00000509339.1 MXD3 5 176735063 promoter blood 30.07 242 ENST00000517813.1 DENND3 8 142194587 promoter blood 13.47 258 ENST00000523369.1 LCP2 5 169685502 promoter blood 9.88 278 ENST00000533815.2 BTNL8 5 180336564 promoter blood 5.72 286 ENST00000538842.1 ATG16L2 11 72527790 promoter blood 6.35 288 ENST00000539932.5 SLC11A1 2 219246926 promoter blood 50.32 294 ENST00000542481.1 ATG16L2 11 72534940 promoter blood 25.18 296 ENST00000543576.5 DENND1C 19 6481798 promoter blood 12.06 306 ENST00000554736.5 GNG2 14 52328042 promoter blood 9.3 311 ENST00000559341.5 MAN2A2 15 91459225 promoter blood 8.61 331 ENST00000566082.1 USB1 16 58049017 promoter blood 6.82 338 ENST00000570439.1 ACAP1 17 7248650 promoter blood 5.27 348 ENST00000574548.1 RNF167 17 4847675 promoter blood 6.4 357 ENST00000581974.1 DHRS13 17 27226541 promoter blood 5.97 376 ENST00000590974.1 LYL1 19 13213975 promoter blood 5.48 388 ENST00000597611.7 FKBP8 19 18654887 promoter blood 9.25 396 ENST00000599180.2 FFAR2 19 35939203 promoter blood 24.79 402 ENST00000601502.1 MYO1F 19 8610602 promoter blood 8.05 415 ENST00000615340.4 RASGRP4 19 38916837 promoter blood 6.88 416 ENST00000616356.4 FCN1 9 137809723 promoter blood 16.99 428 ENST00000221954.6 CEACAM4 19 42133268 junction blood 32.81 435 ENST00000262407.5 ITGA2B 17 42466654 junction blood 12.34 454 ENST00000307395.4 GP9 3 128779693 junction blood 9.72 456 ENST00000310544.8 PHOSPHO1 17 47307830 junction blood 30.92 461 ENST00000324134.10 NLRP12 19 54327140 junction blood 9.17 469 ENST00000338372.6 VSTM1 19 54566998 junction blood 10.71 490 ENST00000380299.3 HBD 11 5255572 junction blood 138.84 500 ENST00000394430.5 RASGRP2 11 64510266 junction blood 17.61 544 ENST00000465984.5 SLC11A1 2 219247098 junction blood 10.54 547 ENST00000466612.5 ABTB1 3 127392451 junction blood 6.18 589 ENST00000484762.1 CSF3R 1 36933423 junction blood 8.26 607 ENST00000488970.1 BTK X 100608858 junction blood 7.4 621 ENST00000496915.1 PREX1 20 47258945 junction blood 5.23 630 ENST00000509314.5 FBXL5 4 15661350 junction blood 10.24 634 ENST00000513001.5 ACSL1 4 185678973 junction blood 17.65 645 ENST00000521442.1 ATP6V1B2 8 20075793 junction blood 8.33 653 ENST00000526387.5 TBC1D10C 11 67171411 junction blood 7.1 666 ENST00000532897.5 MKNK1 1 47037735 junction blood 6.23 667 ENST00000533815.2 BTNL8 5 180336697 junction blood 5.72 674 ENST00000538842.1 ATG16L2 11 72527872 junction blood 6.35 680 ENST00000542481.1 ATG16L2 11 72535167 junction blood 25.18 695 ENST00000559341.5 MAN2A2 15 91459486 junction blood 8.61 708 ENST00000564894.1 RNF166 16 88767670 junction blood 7.9 736 ENST00000581974.1 DHRS13 17 27226145 junction blood 5.97 742 ENST00000585852.5 FMNL1 17 43308054 junction blood 19.81 766 ENST00000597611.7 FKBP8 19 18654719 junction blood 9.25 772 ENST00000599180.2 FFAR2 19 35939281 junction blood 24.79 775 ENST00000599716.5 SHKBP1 19 41082891 junction blood 10.66 776 ENST00000600463.1 IFI30 19 18286032 junction blood 6.41 787 ENST00000614135.4 RASGRP4 19 38916709 junction blood 8.18 789 ENST00000616356.4 FCN1 9 137809615 junction blood 16.99 Columns ID: feature index Transcript: transcript ID Gene: gene name Chr: chromosome Site: coordinate of nucleosome-depleted site (GRCh37) Region: location of nucleosome-depleted site Group: gene group based on its expression in blood and tumor FPKM_(blood): FPKM value in normal blood. Their FPKM values in tumors of 20 cancer types are all <1.

Supplementary Data 1

chr1 11106604 11107500 466_105938_2475(MTOR)_59a 0 — chr1 11108180 11108286 466_105937_2475(MTOR)_58a 0 — chr1 11109289 11109370 466_105936_2475(MTOR)_57a 0 — chr1 11109648 11109729 466_105935_2475(MTOR)_56a 0 — chr1 11112851 11112917 466_105934_2475(MTOR)_55a 0 — chr1 11114317 11114453 466_105933_2475(MTOR)_54a 0 — chr1 11114812 11114887 466_105932_2475(MTOR)_53a 0 — chr1 11115395 11115468 466_105931_2475(MTOR)_52a 0 — chr1 11117003 11117086 466_105930_2475(MTOR)_51a 0 — chr1 11121245 11121368 466_105929_2475(MTOR)_50a 0 — chr1 11121978 11122126 466_105928_2475(MTOR)_49a 0 — chr1 11124497 11124633 466_105927_2475(MTOR)_48a 0 — chr1 11126621 11126796 466_105926_2475(MTOR)_47a 0 — chr1 11127009 11127144 466_105925_2475(MTOR)_46a 0 — chr1 11127623 11127806 466_105924_2475(MTOR)_45a 0 — chr1 11128003 11128126 466_105923_2475(MTOR)_44a 0 — chr1 11128453 11128552 466_105922_2475(MTOR)_43a 0 — chr1 11128854 11128951 466_105921_2475(MTOR)_42a 0 — chr1 11129737 11129838 466_105920_2475(MTOR)_41a 0 — chr1 11130528 11130777 466_105919_2475(MTOR)_40a 0 — chr1 11133079 11133197 466_105918_2475(MTOR)_39a 0 — chr1 11134350 11134466 466_105917_2475(MTOR)_38a 0 — chr1 11139303 11139435 466_105916_2475(MTOR)_37a 0 — chr1 11139528 11139658 466_105915_2475(MTOR)_36a 0 — chr1 11144647 11144755 466_105914_2475(MTOR)_35a 0 — chr1 11144967 11145045 466_105913_2475(MTOR)_34a 0 — chr1 11146675 11146791 466_105912_2475(MTOR)_33a 0 — chr1 11150125 11150226 466_105911_2475(MTOR)_32a 0 — chr1 11157151 11157291 466_105910_2475(MTOR)_31a 0 — chr1 11167441 11167517 466_105909_2475(MTOR)_30a 0 — chr1 11199257 11199403 466_105908_2475(MTOR)_29a 0 — chr1 11199540 11199703 466_105907_2475(MTOR)_28a 0 — chr1 11204560 11204703 466_105906_2475(MTOR)_27a 0 — chr1 11209311 11209458 466_105905_2475(MTOR)_26a 0 — chr1 11210813 11210906 466_105904_2475(MTOR)_25a 0 — chr1 11212311 11212474 466_105903_2475(MTOR)_24a 0 — chr1 11212795 11212908 466_105902_2475(MTOR)_23a 0 — chr1 11213398 11213566 466_105901_2475(MTOR)_22a 0 — chr1 11216147 11216234 466_105900_2475(MTOR)_21a 0 — chr1 11228667 11228918 466_105899_2475(MTOR)_20a 0 — chr1 11230924 11231054 466_105898_2475(MTOR)_19a 0 — chr1 11231299 11231434 466_105897_2475(MTOR)_18a 0 — chr1 11232435 11232528 466_105896_2475(MTOR)_17a 0 — chr1 11233397 11233487 466_105895_2475(MTOR)_16a 0 — chr1 11234142 11234265 466_105894_2475(MTOR)_15a 0 — chr1 11237842 11238048 466_105893_2475(MTOR)_14a 0 — chr1 11238401 11238617 466_105892_2475(MTOR)_13a 0 — chr1 11240302 11240547 466_105891_2475(MTOR)_12a 0 — chr1 11241552 11241681 466_105890_2475(MTOR)_11a 0 — chr1 11243113 11243300 466_105889_2475(MTOR)_10a 0 — chr1 11247624 11247733 466_105888_2475(MTOR)_9a 0 — chr1 11247818 11248094 466_105887_2475(MTOR)_8a 0 — chr1 11253838 11253973 466_105886_2475(MTOR)_7a 0 — chr1 11255991 11256192 466_105885_2475(MTOR)_6a 0 — chr1 11256284 11256302 466_105884_2475(MTOR)_5a 0 — chr1 11256932 11257165 466_105883_2475(MTOR)_4a 0 — chr1 11258484 11258593 466_105882_2475(MTOR)_3a 0 — chr1 11259247 11259415 466_105881_2475(MTOR)_2a 0 — chr1 26696403 26697540 426_4218_8289(ARID1A)_1a 0 — chr1 26729650 26729863 426_4219_8289(ARID1A)_2a 0 — chr1 26731151 26731604 426_4220_8289(ARID1A)_3a 0 — chr1 26732675 26732792 426_4221_8289(ARID1A)_4a 0 — chr1 26760855 26761096 426_4222_8289(ARID1A)_5a 0 — chr1 26761383 26761473 426_4223_8289(ARID1A)_6a 0 — chr1 26762151 26762319 426_4224_8289(ARID1A)_7a 0 — chr1 26762972 26763285 426_4225_8289(ARID1A)_8a 0 — chr1 26766220 26766366 426_4226_8289(ARID1A)_9a 0 — chr1 26766456 26766566 426_4227_8289(ARID1A)_10a 0 — chr1 26767789 26767999 426_4228_8289(ARID1A)_11a 0 — chr1 26771118 26771326 426_4229_8289(ARID1A)_12a 0 — chr1 26772499 26772632 426_4230_8289(ARID1A)_13a 0 — chr1 26772811 26772987 426_4231_8289(ARID1A)_14a 0 — chr1 26773345 26773496 426_4232_8289(ARID1A)_15a 0 — chr1 26773579 26773717 426_4233_8289(ARID1A)_16a 0 — chr1 26773801 26773898 426_4234_8289(ARID1A)_17a 0 — chr1 26774328 26775220 426_4235_8289(ARID1A)_18a 0 — chr1 26775576 26775707 426_4236_8289(ARID1A)_19a 0 — chr1 26779022 26780756 426_4237_8289(ARID1A)_20a 0 — chr1 43337848 43337927 466_106798_4352(MPL)_1a 0 — chr1 43338098 43338231 466_106799_4352(MPL)_2a 0 — chr1 43338541 43338720 466_106800_4352(MPL)_3a 0 — chr1 43339270 43339569 466_106801_4352(MPL)_4a 0 — chr1 43339963 43340126 466_106802_4352(MPL)_5a 0 — chr1 43340386 43340513 466_106803_4352(MPL)_6a 0 — chr1 43346444 43346629 466_106804_4352(MPL)_7a 0 — chr1 43346791 43346934 466_106805_4352(MPL)_8a 0 — chr1 43348842 43349002 466_106806_4352(MPL)_9a 0 — chr1 43349262 43349359 466_106807_4352(MPL)_10a 0 — chr1 43352215 43352303 466_106808_4352(MPL)_11a 0 — chr1 43352517 43352772 466_106809_4352(MPL)_12a 0 — chr1 64834561 64834657 463_81647_3716(JAK1)_26a 0 — chr1 64835395 64835506 463_81646_3716(JAK1)_25a 0 — chr1 64836097 64836215 463_81645_3716(JAK1)_24a 0 — chr1 64837931 64838104 463_81644_3716(JAK1)_23a 0 — chr1 64838464 64838589 463_81643_3716(JAK1)_22a 0 — chr1 64839602 64839795 463_81642_3716(JAK1)_21a 0 — chr1 64841244 64841339 463_81641_3716(JAK1)_20a 0 — chr1 64841450 64841601 463_81640_3716(JAK1)_19a 0 — chr1 64844063 64844215 463_81639_3716(JAK1)_18a 0 — chr1 64844753 64844889 463_81638_3716(JAK1)_17a 0 — chr1 64845512 64845640 463_81637_3716(JAK1)_16a 0 — chr1 64846648 64846736 463_81636_3716(JAK1)_15a 0 — chr1 64847531 64847675 463_81635_3716(JAK1)_14a 0 — chr1 64850803 64850910 463_81634_3716(JAK1)_13a 0 — chr1 64855508 64855698 463_81633_3716(JAK1)_12a 0 — chr1 64857655 64857779 463_81632_3716(JAK1)_11a 0 — chr1 64860104 64860262 463_81631_3716(JAK1)_10a 0 — chr1 64864786 64864972 463_81630_3716(JAK1)_9a 0 — chr1 64866865 64867208 463_81629_3716(JAK1)_8a 0 — chr1 64869310 64869474 463_81628_3716(JAK1)_7a 0 — chr1 64873369 64873523 463_81627_3716(JAK1)_6a 0 — chr1 64879024 64879148 463_81626_3716(JAK1)_5a 0 — chr1 64883276 64883475 463_81625_3716(JAK1)_4a 0 — chr1 64886258 64886341 463_81624_3716(JAK1)_3a 0 — chr1 113391033 113391349 465_103736_260425(MAGI3)_1 0 — chr1 113549514 113549631 465_103737_260425(MAGI3)_2 0 — chr1 113580541 113580661 465_103738_260425(MAGI3)_3 0 — chr1 113585386 113585596 465_103739_260425(MAGI3)_4 0 — chr1 113590483 113590658 465_103740_260425(MAGI3)_5 0 — chr1 113594480 113594560 465_103741_260425(MAGI3)_6 0 — chr1 113614600 113614658 465_103742_260425(MAGI3)_7 0 — chr1 113618531 113618606 465_103743_260425(MAGI3)_8 0 — chr1 113619735 113619830 465_103744_260425(MAGI3)_9 0 — chr1 113622805 113622994 465_103745_260425(MAGI3)_1 0 — chr1 113641910 113642516 465_103746_260425(MAGI3)_11 0 — chr1 113643742 113643774 465_103747_260425(MAGI3)_12 0 — chr1 113646485 113646642 465_103748_260425(MAGI3)_13 0 — chr1 113649236 113649328 465_103749_260425(MAGI3)_14 0 — chr1 113651013 113651206 465_103750_260425(MAGI3)_15 0 — chr1 113653829 113654018 465_103751_260425(MAGI3)_16 0 — chr1 113659079 113659265 465_103752_260425(MAGI3)_17 0 — chr1 113671733 113671836 465_103753_260425(MAGI3)_18 0 — chr1 113672614 113672741 465_103754_260425(MAGI3)_19 0 — chr1 113673321 113673465 465_103755_260425(MAGI3)_20 0 — chr1 113681197 113681336 465_103756_260425(MAGI3)_21 0 — chr1 113682211 113684014 465_103757_260425(MAGI3)_22 0 — chr1 114708534 114708654 469_119576_4893(NRAS)_5 0 — chr1 114709568 114709728 469_119575_4893(NRAS)_4 0 — chr1 114713799 114713978 469_119574_4893(NRAS)_3 0 — chr1 114716049 114716160 469_119573_4893(NRAS)_2 0 — chr1 162711291 162711300 431_48982_4921(DDR2)_4a 0 — chr1 162719036 162719145 431_48983_4921(DDR2)_5a 0 — chr1 162719190 162719214 431_48984_4921(DDR2)_6a 0 — chr1 162741585 162741712 431_48985_4921(DDR2)_7a 0 — chr1 162753094 162753197 431_48986_4921(DDR2)_8a 0 — chr1 162754623 162754855 431_48987_4921(DDR2)_9a 0 — chr1 162755155 162755303 431_48988_4921(DDR2)_10a 0 — chr1 162755663 162755769 431_48989_4921(DDR2)_11a 0 — chr1 162759795 162759979 431_48990_4921(DDR2)_12a 0 — chr1 162761210 162761454 431_48991_4921(DDR2)_13a 0 — chr1 162766000 162766063 431_48992_4921(DDR2)_14a 0 — chr1 162767228 162767359 431_48993_4921(DDR2)_15a 0 — chr1 162770301 162770512 431_48994_4921(DDR2)_16a 0 — chr1 162772023 162772247 431_48995_4921(DDR2)_17a 0 — chr1 162773468 162773596 431_48996_4921(DDR2)_18a 0 — chr1 162775651 162775843 431_48997_4921(DDR2)_19a 0 — chr1 162776135 162776370 431_48998_4921(DDR2)_20a 0 — chr1 162778579 162778729 431_48999_4921(DDR2)_21a 0 — chr1 162780111 162780246 431_49000_4921(DDR2)_22a 0 — chr1 204525327 204525346 466_106137_4194(MDM4)_2a 0 — chr1 204525483 204525596 466_106138_4194(MDM4)_3a 0 — chr1 204526359 204526434 466_106139_4194(MDM4)_4a 0 — chr1 204530683 204530817 466_106140_4194(MDM4)_5a 0 — chr1 204532190 204532246 466_106141_4194(MDM4)_6a 0 — chr1 204537429 204537497 466_106142_4194(MDM4)_7a 0 — chr1 204538208 204538308 466_106143_4194(MDM4)_8a 0 — chr1 204542783 204542944 466_106144_4194(MDM4)_9a 0 — chr1 204544534 204544684 466_106145_4194(MDM4)_10a 0 — chr1 204546796 204546877 466_106146_4194(MDM4)_11a 0 — chr1 204549112 204549682 466_106147_4194(MDM4)_12a 0 — chr10 8055655 8055896 462_69261_2625(GATA3)_4a 0 — chr10 8058304 8058841 462_69262_2625(GATA3)_5a 0 — chr10 8063992 8064138 462_69263_2625(GATA3)_6a 0 — chr10 8069472 8069598 462_69264_2625(GATA3)_7a 0 — chr10 8073738 8074023 462_69265_2625(GATA3)_8a 0 — chr10 43077258 43077331 473_148919_5979(RET)_1a 0 — chr10 43100458 43100722 473_148920_5979(RET)_2a 0 — chr10 43102341 43102629 473_148921_5979(RET)_3a 0 — chr10 43104951 43105193 473_148922_5979(RET)_4a 0 — chr10 43106375 43106571 473_148923_5979(RET)_5a 0 — chr10 43109030 43109230 473_148924_5979(RET)_6a 0 — chr10 43111206 43111465 473_148925_5979(RET)_7a 0 — chr10 43112098 43112224 473_148926_5979(RET)_8a 0 — chr10 43112852 43112963 473_148927_5979(RET)_9a 0 — chr10 43113555 43113675 473_148928_5979(RET)_10a 0 — chr10 43114479 43114736 473_148929_5979(RET)_11a 0 — chr10 43116583 43116731 473_148930_5979(RET)_12a 0 — chr10 43118372 43118480 473_148931_5979(RET)_13a 0 — chr10 43119530 43119745 473_148932_5979(RET)_14a 0 — chr10 43120080 43120203 473_148933_5979(RET)_15a 0 — chr10 43121945 43122016 473_148934_5979(RET)_16a 0 — chr10 43123670 43123808 473_148935_5979(RET)_17a 0 — chr10 43124882 43124982 473_148936_5979(RET)_18a 0 — chr10 43126574 43127504 473_148937_5979(RET)_19a 0 — chr10 43128111 43128269 473_148938_5979(RET)_20a 0 — chr10 87864468 87864547 472_139786_5728(PTEN)_1 0 — chr10 87894024 87894109 472_139787_5728(PTEN)_2 0 — chr10 87925512 87925557 472_139788_5728(PTEN)_3 0 — chr10 87931045 87931089 472_139789_5728(PTEN)_4 0 — chr10 87933012 87933251 472_139790_5728(PTEN)_5 0 — chr10 87952117 87952259 472_139791_5728(PTEN)_6 0 — chr10 87957852 87958019 472_139792_5728(PTEN)_7 0 — chr10 87960893 87961118 472_139793_5728(PTEN)_8 0 — chr10 87965286 87965472 472_139794_5728(PTEN)_9 0 — chr10 121479580 121480021 461_60371_2263(FGFR2)_21a 0 — chr10 121481850 121482177 461_60370_2263(FGFR2)_20a 0 — chr10 121483697 121483803 461_60369_2263(FGFR2)_19a 0 — chr10 121485394 121485532 461_60368_2263(FGFR2)_18a 0 — chr10 121487353 121487424 461_60367_2263(FGFR2)_17a 0 — chr10 121487990 121488113 461_60366_2263(FGFR2)_16a 0 — chr10 121496531 121496722 461_60365_2263(FGFR2)_15a 0 — chr10 121498494 121498605 461_60364_2263(FGFR2)_14a 0 — chr10 121500825 121500947 461_60363_2263(FGFR2)_13a 0 — chr10 121503789 121503941 461_60362_2263(FGFR2)_12a 0 — chr10 121515116 121515319 461_60361_2263(FGFR2)_11a 0 — chr10 121517318 121517463 461_60360_2263(FGFR2)_10a 0 — chr10 121518681 121518829 461_60359_2263(FGFR2)_9a 0 — chr10 121519978 121520169 461_60358_2263(FGFR2)_8a 0 — chr10 121538591 121538715 461_60357_2263(FGFR2)_7a 0 — chr10 121551289 121551459 461_60356_2263(FGFR2)_6a 0 — chr10 121564501 121564579 461_60355_2263(FGFR2)_5a 0 — chr10 121565437 121565704 461_60354_2263(FGFR2)_4a 0 — chr10 121593708 121593817 461_60353_2263(FGFR2)_3a 0 — chr11 532588 532755 463_79038_3265(HRAS)_6a 0 — chr11 533276 533358 463_79037_3265(HRAS)_5a 0 — chr11 533452 533612 463_79036_3265(HRAS)_4a 0 — chr11 533765 533944 463_79035_3265(HRAS)_3a 0 — chr11 534211 534322 463_79034_3265(HRAS)_2a 0 — chr11 108227624 108227696 427_14211_472(ATM)_5 0 — chr11 108227775 108227888 427_14212_472(ATM)_6 0 — chr11 108229177 108229323 427_14213_472(ATM)_7 0 — chr11 108235669 108235834 427_14214_472(ATM)_8 0 — chr11 108243952 108244118 427_14215_472(ATM)_9 0 — chr11 108244787 108245026 427_14216_472(ATM)_10 0 — chr11 108246543 108246560 427_14217_472(ATM)_11 0 — chr11 108246963 108247127 427_14218_472(ATM)_12 0 — chr11 108248932 108249102 427_14219_472(ATM)_13 0 — chr11 108250700 108251072 427_14220_472(ATM)_14 0 — chr11 108251836 108252031 427_14221_472(ATM)_15 0 — chr11 108252816 108252912 427_14222_472(ATM)_16 0 — chr11 108253813 108254039 427_14223_472(ATM)_17 0 — chr11 108256214 108256340 427_14224_472(ATM)_18 0 — chr11 108257480 108257606 427_14225_472(ATM)_19 0 — chr11 108258985 108259075 427_14226_472(ATM)_20 0 — chr11 108267170 108267342 427_14227_472(ATM)_21 0 — chr11 108268409 108268609 427_14228_472(ATM)_22 0 — chr11 108271063 108271146 427_14229_472(ATM)_23 0 — chr11 108271250 108271406 427_14230_472(ATM)_24 0 — chr11 108272531 108272607 427_14231_472(ATM)_25 0 — chr11 108272721 108272852 427_14232_472(ATM)_26 0 — chr11 108279490 108279608 427_14233_472(ATM)_27 0 — chr11 108280994 108281168 427_14234_472(ATM)_28 0 — chr11 108282709 108282879 427_14235_472(ATM)_29 0 — chr11 108284226 108284473 427_14236_472(ATM)_30 0 — chr11 108287599 108287715 427_14237_472(ATM)_31 0 — chr11 108288976 108289103 427_14238_472(ATM)_32 0 — chr11 108289601 108289801 427_14239_472(ATM)_33 0 — chr11 108292618 108292793 427_14240_472(ATM)_34 0 — chr11 108293312 108293477 427_14241_472(ATM)_35 0 — chr11 108294926 108295059 427_14242_472(ATM)_36 0 — chr11 108297286 108297382 427_14243_472(ATM)_37 0 — chr11 108299713 108299885 427_14244_472(ATM)_38 0 — chr11 108301647 108301789 427_14245_472(ATM)_39 0 — chr11 108302852 108303029 427_14246_472(ATM)_40 0 — chr11 108304674 108304852 427_14247_472(ATM)_41 0 — chr11 108307896 108307984 427_14248_472(ATM)_42 0 — chr11 108310159 108310315 427_14249_472(ATM)_43 0 — chr11 108312410 108312498 427_14250_472(ATM)_44 0 — chr11 108315822 108315911 427_14251_472(ATM)_45 0 — chr11 108316010 108316113 427_14252_472(ATM)_46 0 — chr11 108317372 108317521 427_14253_472(ATM)_47 0 — chr11 108319953 108320058 427_14254_472(ATM)_48 0 — chr11 108321300 108321420 427_14255_472(ATM)_49 0 — chr11 108325309 108325544 427_14256_472(ATM)_50 0 — chr11 108326057 108326225 427_14257_472(ATM)_51 0 — chr11 108327644 108327758 427_14258_472(ATM)_52 0 — chr11 108329020 108329238 427_14259_472(ATM)_53 0 — chr11 108330213 108330421 427_14260_472(ATM)_54 0 — chr11 108331443 108331557 427_14261_472(ATM)_55 0 — chr11 108331878 108332037 427_14262_472(ATM)_56 0 — chr11 108332761 108332900 427_14263_472(ATM)_57 0 — chr11 108333885 108333968 427_14264_472(ATM)_58 0 — chr11 108334968 108335109 427_14265_472(ATM)_59 0 — chr11 108335844 108335961 427_14266_472(ATM)_60 0 — chr11 108343221 108343371 427_14267_472(ATM)_61 0 — chr11 108345742 108345908 427_14268_472(ATM)_62 0 — chr11 108347278 108347365 427_14269_472(ATM)_63 0 — chr11 108353765 108353880 427_14270_472(ATM)_64 0 — chr11 108354810 108354874 427_14271_472(ATM)_65 0 — chr11 108365081 108365218 427_14272_472(ATM)_66 0 — chr11 108365324 108365508 427_14273_472(ATM)_67 0 — chr11 118898414 118899508 427_22416_283149(BCL9L)_10 0 — chr11 118899916 118900198 427_22415_283149(BCL9L)_9 0 — chr11 118900618 118902908 427_22414_283149(BCL9L)_8 0 — chr11 118902989 118903074 427_22413_283149(BCL9L)_7 0 — chr11 118903235 118903452 427_22412_283149(BCL9L)_6 0 — chr11 118907482 118907602 427_22411_283149(BCL9L)_5 0 — chr11 118908269 118908655 427_22410_283149(BCL9L)_4 0 — chr11 118909913 118909939 427_22409_283149(BCL9L)_3 0 — chr12 6570675 6570693 429_33493_1108(CHD4)_40 0 — chr12 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6592392 6592566 429_33472_1108(CHD4)_19 0 — chr12 6592695 6592817 429_33471_1108(CHD4)_18 0 — chr12 6593090 6593228 429_33470_1108(CHD4)_17 0 — chr12 6593415 6593616 429_33469_1108(CHD4)_16 0 — chr12 6594458 6594650 429_33468_1108(CHD4)_15 0 — chr12 6595333 6595430 429_33467_1108(CHD4)_14 0 — chr12 6596005 6596137 429_33466_1108(CHD4)_13 0 — chr12 6597893 6598099 429_33465_1108(CHD4)_12 0 — chr12 6598221 6598425 429_33464_1108(CHD4)_11 0 — chr12 6599772 6600012 429_33463_1108(CHD4)_10 0 — chr12 6600216 6600395 429_33462_1108(CHD4)_9 0 — chr12 6600533 6600669 429_33461_1108(CHD4)_8 0 — chr12 6600925 6601053 429_33460_1108(CHD4)_7 0 — chr12 6601288 6601530 429_33459_1108(CHD4)_6 0 — chr12 6601647 6601766 429_33458_1108(CHD4)_5 0 — chr12 6601959 6602175 429_33457_1108(CHD4)_4 0 — chr12 6602375 6602497 429_33456_1108(CHD4)_3 0 — chr12 6606273 6606373 429_33455_1108(CHD4)_2 0 — chr12 12717839 12718314 428_25760_1027(CDKN1B)_1a 0 — chr12 12718824 12718946 428_25761_1027(CDKN1B)_2a 0 — chr12 25209510 25209911 464_89190_3845(KRAS)_6 0 — chr12 25215149 25215560 464_89189_3845(KRAS)_5 0 — chr12 25225613 25225773 464_89188_3845(KRAS)_4 0 — chr12 25227233 25227412 464_89187_3845(KRAS)_3 0 — chr12 25245273 25245395 464_89186_3845(KRAS)_2 0 — chr12 56080300 56080382 461_58650_2065(ERBB3)_1a 0 — chr12 56080300 56080382 461_58650_2065(ERBB3)_1a 0 — chr12 56083750 56083902 461_58651_2065(ERBB3)_2a 0 — chr12 56083750 56083902 461_58651_2065(ERBB3)_2a 0 — chr12 56084994 56085617 461_58652_2065(ERBB3)_3a 0 — chr12 56084994 56085617 461_58652_2065(ERBB3)_3a 0 — chr12 56086530 56086656 461_58653_2065(ERBB3)_4a 0 — chr12 56086530 56086656 461_58653_2065(ERBB3)_4a 0 — chr12 56087576 56087642 461_58654_2065(ERBB3)_5a 0 — chr12 56087576 56087642 461_58654_2065(ERBB3)_5a 0 — chr12 56087794 56087913 461_58655_2065(ERBB3)_6a 0 — chr12 56087794 56087913 461_58655_2065(ERBB3)_6a 0 — chr12 56088020 56088162 461_58656_2065(ERBB3)_7a 0 — chr12 56088020 56088162 461_58656_2065(ERBB3)_7a 0 — chr12 56088542 56088656 461_58657_2065(ERBB3)_8a 0 — chr12 56088542 56088656 461_58657_2065(ERBB3)_8a 0 — chr12 56088747 56088868 461_58658_2065(ERBB3)_9a 0 — chr12 56088747 56088868 461_58658_2065(ERBB3)_9a 0 — chr12 56092746 56092820 461_58659_2065(ERBB3)_10a 0 — chr12 56092746 56092820 461_58659_2065(ERBB3)_10a 0 — chr12 56092985 56093076 461_58660_2065(ERBB3)_11a 0 — chr12 56092985 56093076 461_58660_2065(ERBB3)_11a 0 — chr12 56093344 56093550 461_58755_2065(ERBB3)_12a 0 — chr12 56093344 56093550 461_58755_2065(ERBB3)_12a 0 — chr12 56093763 56093896 461_58756_2065(ERBB3)_13a 0 — chr12 56093763 56093896 461_58756_2065(ERBB3)_13a 0 — chr12 56094098 56094189 461_58757_2065(ERBB3)_14a 0 — chr12 56094098 56094189 461_58757_2065(ERBB3)_14a 0 — chr12 56094401 56094556 461_58758_2065(ERBB3)_15a 0 — chr12 56094401 56094556 461_58758_2065(ERBB3)_15a 0 — chr12 56095256 56095310 461_58759_2065(ERBB3)_16a 0 — chr12 56095256 56095310 461_58759_2065(ERBB3)_16a 0 — chr12 56095664 56095806 461_58760_2065(ERBB3)_17a 0 — chr12 56095664 56095806 461_58760_2065(ERBB3)_17a 0 — chr12 56096502 56096622 461_58761_2065(ERBB3)_18a 0 — chr12 56096502 56096622 461_58761_2065(ERBB3)_18a 0 — chr12 56096747 56096846 461_58762_2065(ERBB3)_19a 0 — chr12 56096747 56096846 461_58762_2065(ERBB3)_19a 0 — chr12 56097044 56097230 461_58763_2065(ERBB3)_20a 0 — chr12 56097044 56097230 461_58763_2065(ERBB3)_20a 0 — chr12 56097784 56097940 461_58764_2065(ERBB3)_21a 0 — chr12 56097784 56097940 461_58764_2065(ERBB3)_21a 0 — chr12 56098499 56098575 461_58765_2065(ERBB3)_22a 0 — chr12 56098499 56098575 461_58765_2065(ERBB3)_22a 0 — chr12 56098758 56098905 461_58766_2065(ERBB3)_23a 0 — chr12 56098758 56098905 461_58766_2065(ERBB3)_23a 0 — chr12 56099647 56099745 461_58767_2065(ERBB3)_24a 0 — chr12 56099647 56099745 461_58767_2065(ERBB3)_24a 0 — chr12 56099837 56100029 461_58768_2065(ERBB3)_25a 0 — chr12 56099837 56100029 461_58768_2065(ERBB3)_25a 0 — chr12 56100173 56100245 461_58769_2065(ERBB3)_26a 0 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472_140050_5781(PTPN11)_2a 0 — chr12 112450317 112450512 472_140051_5781(PTPN11)_3a 0 — chr12 112453194 112453387 472_140052_5781(PTPN11)_4a 0 — chr12 112454563 112454680 472_140053_5781(PTPN11)_5a 0 — chr12 112455949 112456063 472_140054_5781(PTPN11)_6a 0 — chr12 112472943 112473040 472_140055_5781(PTPN11)_7a 0 — chr12 112477650 112477730 472_140056_5781(PTPN11)_8a 0 — chr12 112477856 112478015 472_140057_5781(PTPN11)_9a 0 — chr12 112482073 112482205 472_140058_5781(PTPN11)_10a 0 — chr12 112486474 112486923 472_140059_5781(PTPN11)_11a 0 — chr12 112488442 112488510 472_140060_5781(PTPN11)_12a 0 — chr12 112489023 112489175 472_140061_5781(PTPN11)_13a 0 — chr12 112502143 112502256 472_140062_5781(PTPN11)_14a 0 — chr12 112504694 112504764 472_140063_5781(PTPN11)_15a 0 — chr12 120978768 120979094 463_81838_6927(HNF1A)_1 0 — chr12 120988832 120989032 463_81839_6927(HNF1A)_2 0 — chr12 120993519 120993706 463_81840_6927(HNF1A)_3 0 — chr12 120994163 120994405 463_81841_6927(HNF1A)_4 0 — chr12 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132642996 470_129077_5426(POLE)_36 0 — chr12 132643223 132643330 470_129076_5426(POLE)_35 0 — chr12 132643406 132643560 470_129075_5426(POLE)_34 0 — chr12 132643836 132643977 470_129074_5426(POLE)_33 0 — chr12 132648928 132649072 470_129073_5426(POLE)_32 0 — chr12 132649305 132649515 470_129072_5426(POLE)_31 0 — chr12 132649676 132649889 470_129071_5426(POLE)_30 0 — chr12 132657135 132657258 470_129070_5426(POLE)_29 0 — chr12 132657348 132657429 470_129069_5426(POLE)_28 0 — chr12 132657867 132657970 470_129068_5426(POLE)_27 0 — chr12 132659294 132659509 470_129067_5426(POLE)_26 0 — chr12 132660968 132661164 470_129066_5426(POLE)_25 0 — chr12 132661526 132661684 470_129065_5426(POLE)_24 0 — chr12 132664003 132664148 470_129064_5426(POLE)_23 0 — chr12 132664369 132664462 470_129063_5426(POLE)_22 0 — chr12 132665301 132665450 470_129062_5426(POLE)_21 0 — chr12 132667502 132667648 470_129061_5426(POLE)_20 0 — chr12 132668355 132668502 470_129060_5426(POLE)_19 0 — chr12 132668634 132668737 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58415577 473_154854_54894(RNF43)_2 0 — chr17 72121391 72121822 474_160949_6662(SOX9)_1 0 — chr17 72122718 72122972 474_160950_6662(SOX9)_2 0 — chr17 72123542 72124387 474_160951_6662(SOX9)_3 0 — chr18 47841826 47841950 474_158715_4087(SMAD2)_13a 0 — chr18 47845339 47845484 474_158714_4087(SMAD2)_12a 0 — chr18 47845662 47845800 474_158713_4087(SMAD2)_11a 0 — chr18 47848474 47848687 474_158712_4087(SMAD2)_10a 0 — chr18 47851273 47851327 474_158711_4087(SMAD2)_9a 0 — chr18 47865058 47865133 474_158710_4087(SMAD2)_8a 0 — chr18 47868322 47868457 474_158709_4087(SMAD2)_7a 0 — chr18 47869242 47869436 474_158708_4087(SMAD2)_6a 0 — chr18 47870474 47870564 474_158707_4087(SMAD2)_5a 0 — chr18 47896520 47896803 474_158706_4087(SMAD2)_4a 0 — chr18 51047046 51047295 474_158716_4089(SMAD4)_2 0 — chr18 51048685 51048860 474_158717_4089(SMAD4)_3 0 — chr18 51049294 51049324 474_158718_4089(SMAD4)_4 0 — chr18 51054780 51054993 474_158719_4089(SMAD4)_5 0 — chr18 51058124 51058244 474_158720_4089(SMAD4)_6 0 — chr18 51058339 51058456 474_158721_4089(SMAD4)_7 0 — chr18 51059865 51059916 474_158722_4089(SMAD4)_8 0 — chr18 51065422 51065606 474_158723_4089(SMAD4)_9 0 — chr18 51067018 51067187 474_158724_4089(SMAD4)_10 0 — chr18 51076637 51076776 474_158725_4089(SMAD4)_11 0 — chr18 51077306 51077419 474_158726_4089(SMAD4)_12 0 — chr18 51078255 51078467 474_158727_4089(SMAD4)_13 0 — chr18 52340787 52340878 431_46002_1630(DCC)_1 0 — chr18 52752053 52752374 431_46003_1630(DCC)_2 0 — chr18 52906043 52906328 431_46004_1630(DCC)_3 0 — chr18 52923706 52923857 431_46005_1630(DCC)_4 0 — chr18 52925233 52925370 431_46006_1630(DCC)_5 0 — chr18 53063304 53063459 431_46007_1630(DCC)_6 0 — chr18 53066045 53066166 431_46008_1630(DCC)_7 0 — chr18 53157355 53157512 431_46009_1630(DCC)_8 0 — chr18 53178961 53179116 431_46010_1630(DCC)_9 0 — chr18 53205215 53205364 431_46011_1630(DCC)_10 0 — chr18 53207678 53207817 431_46012_1630(DCC)_11 0 — chr18 53215547 53215597 431_46013_1630(DCC)_12 0 — chr18 53305577 53305719 431_46014_1630(DCC)_13 0 — chr18 53322046 53322157 431_46015_1630(DCC)_14 0 — chr18 53339712 53339907 431_46016_1630(DCC)_15 0 — chr18 53386042 53386138 431_46017_1630(DCC)_16 0 — chr18 53391654 53391887 431_46018_1630(DCC)_17 0 — chr18 53397307 53397446 431_46019_1630(DCC)_18 0 — chr18 53402785 53402893 431_46020_1630(DCC)_19 0 — chr18 53410451 53410646 431_46021_1630(DCC)_20 0 — chr18 53416123 53416156 431_46022_1630(DCC)_21 0 — chr18 53435143 53435209 431_46023_1630(DCC)_22 0 — chr18 53450499 53450662 431_46024_1630(DCC)_23 0 — chr18 53459231 53459458 431_46025_1630(DCC)_24 0 — chr18 53467893 53468010 431_46026_1630(DCC)_25 0 — chr18 53486796 53486958 431_46027_1630(DCC)_26 0 — chr18 53499297 53499510 431_46028_1630(DCC)_27 0 — chr18 53526616 53526759 431_46029_1630(DCC)_28 0 — chr18 53530563 53530653 431_46030_1630(DCC)_29 0 — chr19 1206913 1207203 475_170587_6794(STK11)_1a 0 — chr19 1218416 1218500 475_170588_6794(STK11)_2a 0 — chr19 1219323 1219413 475_170589_6794(STK11)_3a 0 — chr19 1220372 1220505 475_170590_6794(STK11)_4a 0 — chr19 1220580 1220717 475_170591_6794(STK11)_5a 0 — chr19 1221212 1221340 475_170592_6794(STK11)_6a 0 — chr19 1221948 1222006 475_170593_6794(STK11)_7a 0 — chr19 1222984 1223172 475_170594_6794(STK11)_8a 0 — chr19 1223637 1226446 475_170595_6794(STK11)_9a 0 — chr19 1226453 1226663 475_170596_6794(STK11)_10a 0 — chr19 1227592 1228082 475_170597_6794(STK11)_11a 0 — chr19 2164184 2164265 431_55601_84444(DOT1L)_1 0 — chr19 2180712 2180756 431_55602_84444(DOT1L)_2 0 — chr19 2185854 2185929 431_55603_84444(DOT1L)_3 0 — chr19 2189731 2189795 431_55604_84444(DOT1L)_4 0 — chr19 2191011 2191240 431_55605_84444(DOT1L)_5 0 — chr19 2193688 2193783 431_55606_84444(DOT1L)_6 0 — chr19 2194514 2194577 431_55607_84444(DOT1L)_7 0 — chr19 2199883 2199939 431_55608_84444(DOT1L)_8 0 — chr19 2202699 2202779 431_55609_84444(DOT1L)_9 0 — chr19 2206728 2206797 431_55610_84444(DOT1L)_10 0 — chr19 2207573 2207680 431_55611_84444(DOT1L)_11 0 — chr19 2208934 2208976 431_55612_84444(DOT1L)_12 0 — chr19 2210399 2210510 431_55613_84444(DOT1L)_13 0 — chr19 2210620 2210855 431_55614_84444(DOT1L)_14 0 — chr19 2211098 2211212 431_55615_84444(DOT1L)_15 0 — chr19 2211750 2211842 431_55616_84444(DOT1L)_16 0 — chr19 2213538 2213640 431_55617_84444(DOT1L)_17 0 — chr19 2213848 2213986 431_55618_84444(DOT1L)_18 0 — chr19 2214470 2214596 431_55619_84444(DOT1L)_19 0 — chr19 2216280 2216765 431_55620_84444(DOT1L)_20 0 — chr19 2216954 2217090 431_55621_84444(DOT1L)_21 0 — chr19 2217771 2217918 431_55622_84444(DOT1L)_22 0 — chr19 2220107 2220222 431_55623_84444(DOT1L)_23 0 — chr19 2221975 2222559 431_55624_84444(DOT1L)_24 0 — chr19 2223280 2223486 431_55625_84444(DOT1L)_25 0 — chr19 2225387 2225452 431_55626_84444(DOT1L)_26 0 — chr19 2226182 2227127 431_55627_84444(DOT1L)_27 0 — chr19 2227736 2229792 431_55628_84444(DOT1L)_28 0 — chr19 3094651 3094787 462_70067_2767(GNA11)_1 0 — chr19 3110148 3110333 462_70068_2767(GNA11)_2 0 — chr19 3113329 3113484 462_70069_2767(GNA11)_3 0 — chr19 3114943 3115072 462_70070_2767(GNA11)_4 0 — chr19 3118923 3119053 462_70071_2767(GNA11)_5 0 — chr19 3119205 3119359 462_70072_2767(GNA11)_6 0 — chr19 3120988 3121179 462_70073_2767(GNA11)_7 0 — chr19 12938679 12938770 428_24220_811(CALR)_1 0 — chr19 12939133 12939235 428_24221_811(CALR)_2 0 — chr19 12939427 12939631 428_24222_811(CALR)_3 0 — chr19 12940052 12940147 428_24223_811(CALR)_4 0 — chr19 12940242 12940452 428_24224_811(CALR)_5 0 — chr19 12940540 12940654 428_24225_811(CALR)_6 0 — chr19 12940743 12940887 428_24226_811(CALR)_7 0 — chr19 12943536 12943629 428_24227_811(CALR)_8 0 — chr19 12943712 12943913 428_24228_811(CALR)_9 0 — chr19 17826742 17826910 463_81766_3718(JAK3)_24a 0 — chr19 17830107 17830218 463_81765_3718(JAK3)_23a 0 — chr19 17830502 17830620 463_81764_3718(JAK3)_22a 0 — chr19 17831227 17831400 463_81763_3718(JAK3)_21a 0 — chr19 17831673 17831798 463_81762_3718(JAK3)_20a 0 — chr19 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470_129034_5424(POLD1)_20 0 — chr19 50415437 50415590 470_129035_5424(POLD1)_21 0 — chr19 50415723 50415826 470_129036_5424(POLD1)_22 0 — chr19 50416395 50416528 470_129037_5424(POLD1)_23 0 — chr19 50416609 50416723 470_129038_5424(POLD1)_24 0 — chr19 50417044 50417097 470_129039_5424(POLD1)_25 0 — chr19 50417171 50417269 470_129040_5424(POLD1)_26 0 — chr19 50417841 50417947 470_129041_5424(POLD1)_27 0 — chr2 29193223 29193922 426_1998_238(ALK)_29 0 — chr2 29196769 29196860 426_1997_238(ALK)_28 0 — chr2 29197541 29197676 426_1996_238(ALK)_27 0 — chr2 29207170 29207272 426_1995_238(ALK)_26 0 — chr2 29209785 29209878 426_1994_238(ALK)_25 0 — chr2 29213983 29214081 426_1993_238(ALK)_24 0 — chr2 29220705 29220835 426_1992_238(ALK)_23 0 — chr2 29222343 29222408 426_1991_238(ALK)_22 0 — chr2 29222516 29222607 426_1990_238(ALK)_21 0 — chr2 29223341 29223528 426_1989_238(ALK)_20 0 — chr2 29225460 29225565 426_1988_238(ALK)_19 0 — chr2 29226921 29227074 426_1987_238(ALK)_18 0 — chr2 29227573 29227672 426_1986_238(ALK)_17 0 — chr2 29228883 29229066 426_1985_238(ALK)_16 0 — chr2 29232303 29232448 426_1984_238(ALK)_15 0 — chr2 29233564 29233696 426_1983_238(ALK)_14 0 — chr2 29239679 29239830 426_1982_238(ALK)_13 0 — chr2 29251104 29251267 426_1981_238(ALK)_12 0 — chr2 29275098 29275227 426_1980_238(ALK)_11 0 — chr2 29275401 29275496 426_1979_238(ALK)_10 0 — chr2 29296887 29297057 426_1978_238(ALK)_9 0 — chr2 29318303 29318404 426_1977_238(ALK)_8 0 — chr2 29320750 29320882 426_1976_238(ALK)_7 0 — chr2 29328349 29328481 426_1975_238(ALK)_6 0 — chr2 29383731 29383859 426_1974_238(ALK)_5 0 — chr2 29531914 29532116 426_1973_238(ALK)_4 0 — chr2 29694849 29695014 426_1972_238(ALK)_3 0 — chr2 29717577 29717697 426_1971_238(ALK)_2 0 — chr2 29919992 29920659 426_1970_238(ALK)_1 0 — chr2 43224318 43225752 477_180793_678(ZFP36L2)_2 0 — chr2 43226264 43226315 477_180792_678(ZFP36L2)_1 0 — chr2 147845152 147845207 426_921_92(ACVR2A)_2 0 — chr2 147896300 147896508 426_922_92(ACVR2A)_3 0 — chr2 147899457 147899567 426_923_92(ACVR2A)_4 0 — chr2 147899743 147899898 426_924_92(ACVR2A)_5 0 — chr2 147915190 147915334 426_925_92(ACVR2A)_6 0 — chr2 147917282 147917426 426_926_92(ACVR2A)_7 0 — chr2 147918446 147918592 426_927_92(ACVR2A)_8 0 — chr2 147920229 147920344 426_928_92(ACVR2A)_9 0 — chr2 147922972 147923111 426_929_92(ACVR2A)_10 0 — chr2 147926030 147926161 426_930_92(ACVR2A)_11 0 — chr2 147927079 147927274 426_931_92(ACVR2A)_12 0 — chr2 208237078 208237169 463_79499_3417(IDH1)_13a 0 — chr2 208239070 208239233 463_79498_3417(IDH1)_12a 0 — chr2 208239862 208240003 463_79497_3417(IDH1)_11a 0 — chr2 208241993 208242145 463_79496_3417(IDH1)_10a 0 — chr2 208243426 208243604 463_79495_3417(IDH1)_9a 0 — chr2 208245318 208245424 463_79494_3417(IDH1)_8a 0 — chr2 208248368 208248660 463_79493_3417(IDH1)_7a 0 — chr2 208251429 208251551 463_79492_3417(IDH1)_6a 0 — chr2 211383614 211384060 461_58800_2066(ERBB4)_29a 0 — chr2 211386852 211387150 461_58799_2066(ERBB4)_28a 0 — chr2 211387944 211387992 461_58798_2066(ERBB4)_27a 0 — chr2 211420440 211420611 461_58797_2066(ERBB4)_26a 0 — chr2 211422006 211422104 461_58796_2066(ERBB4)_25a 0 — chr2 211424154 211424301 461_58795_2066(ERBB4)_24a 0 — chr2 211428407 211428483 461_58794_2066(ERBB4)_23a 0 — chr2 211430944 211431100 461_58793_2066(ERBB4)_22a 0 — chr2 211561902 211562088 461_58792_2066(ERBB4)_21a 0 — chr2 211619176 211619275 461_58791_2066(ERBB4)_20a 0 — chr2 211623921 211624044 461_58790_2066(ERBB4)_19a 0 — chr2 211630461 211630594 461_58789_2066(ERBB4)_18a 0 — chr2 211657753 211657828 461_58788_2066(ERBB4)_17a 0 — chr2 211657949 211657994 461_58787_2066(ERBB4)_16a 0 — chr2 211665322 211665477 461_58786_2066(ERBB4)_15a 0 — chr2 211673163 211673257 461_58785_2066(ERBB4)_14a 0 — chr2 211679051 211679184 461_58784_2066(ERBB4)_13a 0 — chr2 211701966 211702166 461_58783_2066(ERBB4)_12a 0 — chr2 211704103 211704194 461_58782_2066(ERBB4)_11a 0 — chr2 211705317 211705391 461_58781_2066(ERBB4)_10a 0 — chr2 211712049 211712176 461_58780_2066(ERBB4)_9a 0 — chr2 211713534 211713648 461_58779_2066(ERBB4)_8a 0 — chr2 211722392 211722534 461_58778_2066(ERBB4)_7a 0 — chr2 211725075 211725194 461_58777_2066(ERBB4)_6a 0 — chr2 211750638 211750704 461_58776_2066(ERBB4)_5a 0 — chr2 211788024 211788159 461_58775_2066(ERBB4)_4a 0 — chr2 211947429 211947616 461_58774_2066(ERBB4)_3a 0 — chr2 212124751 212124903 461_58773_2066(ERBB4)_2a 0 — chr2 212538448 212538530 461_58772_2066(ERBB4)_1a 0 — chr20 37384153 37384403 475_169917_6714(SRC)_5a 0 — chr20 37386074 37386174 475_169918_6714(SRC)_6a 0 — chr20 37393894 37393993 475_169919_6714(SRC)_7a 0 — chr20 37394173 37394277 475_169920_6714(SRC)_8a 0 — chr20 37396161 37396311 475_169921_6714(SRC)_9a 0 — chr20 37397698 37397854 475_169922_6714(SRC)_10a 0 — chr20 37400114 37400294 475_169923_6714(SRC)_11a 0 — chr20 37401601 37401678 475_169924_6714(SRC)_12a 0 — chr20 37402434 37402588 475_169925_6714(SRC)_13a 0 — chr20 37402748 37402880 475_169926_6714(SRC)_14a 0 — 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chr7 140787547 140787584 427_15638_673(BRAF)_9 0 — chr7 140794307 140794467 427_15637_673(BRAF)_8 0 — chr7 140800361 140800481 427_15636_673(BRAF)_7 0 — chr7 140801411 140801560 427_15635_673(BRAF)_6 0 — chr7 140807959 140808062 427_15634_673(BRAF)_5 0 — chr7 140808891 140808995 427_15633_673(BRAF)_4 0 — chr7 140834608 140834872 427_15632_673(BRAF)_3 0 — chr7 140850110 140850212 427_15631_673(BRAF)_2 0 — chr7 140924565 140924756 427_15630_673(BRAF)_1 0 — chr7 148807645 148807706 461_59365_2146(EZH2)_22 0 — chr7 148809070 148809155 461_59364_2146(EZH2)_21 0 — chr7 148809309 148809390 461_59363_2146(EZH2)_20 0 — chr7 148810332 148810414 461_59362_2146(EZH2)_19 0 — chr7 148811624 148811720 461_59361_2146(EZH2)_18 0 — chr7 148813958 148814137 461_59360_2146(EZH2)_17 0 — chr7 148814913 148815039 461_59359_2146(EZH2)_16 0 — chr7 148815505 148815546 461_59358_2146(EZH2)_15 0 — chr7 148816683 148816778 461_59357_2146(EZH2)_14 0 — chr7 148817221 148817391 461_59356_2146(EZH2)_13 0 — chr7 148817876 148818117 461_59355_2146(EZH2)_12 0 — chr7 148819595 148819687 461_59354_2146(EZH2)_11 0 — chr7 148826453 148826632 461_59353_2146(EZH2)_10 0 — chr7 148827163 148827266 461_59352_2146(EZH2)_9 0 — chr7 148828739 148828880 461_59351_2146(EZH2)_8 0 — chr7 148829727 148829848 461_59350_2146(EZH2)_7 0 — chr7 148832633 148832750 461_59349_2146(EZH2)_6 0 — chr7 148846469 148846598 461_59348_2146(EZH2)_5 0 — chr7 148847181 148847305 461_59347_2146(EZH2)_4 0 — chr7 148850453 148850470 461_59346_2146(EZH2)_3 0 — chr7 152136831 152136924 464_95024_58508(KMT2C)_61 0 — chr7 152138795 152138904 464_95023_58508(KMT2C)_60 0 — chr7 152139185 152139259 464_95022_58508(KMT2C)_59 0 — chr7 152139674 152139791 464_95021_58508(KMT2C)_58 0 — chr7 152144712 152144881 464_95020_58508(KMT2C)_57 0 — chr7 152145152 152145295 464_95019_58508(KMT2C)_56 0 — chr7 152146598 152146735 464_95018_58508(KMT2C)_55 0 — chr7 152148032 152149152 464_95017_58508(KMT2C)_54 0 — chr7 152150899 152151007 464_95016_58508(KMT2C)_53 0 — chr7 152151441 152151581 464_95015_58508(KMT2C)_52 0 — chr7 152152704 152152954 464_95014_58508(KMT2C)_51 0 — chr7 152154009 152154146 464_95013_58508(KMT2C)_50 0 — chr7 152154266 152154445 464_95012_58508(KMT2C)_49 0 — chr7 152155909 152156057 464_95011_58508(KMT2C)_48 0 — chr7 152156204 152156346 464_95010_58508(KMT2C)_47 0 — chr7 152157760 152157925 464_95009_58508(KMT2C)_46 0 — chr7 152158856 152159072 464_95008_58508(KMT2C)_45 0 — chr7 152162116 152163826 464_95007_58508(KMT2C)_44 0 — chr7 152167145 152167378 464_95006_58508(KMT2C)_43 0 — chr7 152169185 152169249 464_95005_58508(KMT2C)_42 0 — chr7 152171263 152171342 464_95004_58508(KMT2C)_41 0 — chr7 152174130 152174242 464_95003_58508(KMT2C)_40 0 — chr7 152176190 152178010 464_95002_58508(KMT2C)_39 0 — chr7 152179833 152180126 464_95001_58508(KMT2C)_38 0 — chr7 152180710 152182594 464_95000_58508(KMT2C)_37 0 — chr7 152182973 152183156 464_94999_58508(KMT2C)_36 0 — chr7 152185557 152185631 464_94998_58508(KMT2C)_35 0 — chr7 152187261 152187476 464_94997_58508(KMT2C)_34 0 — chr7 152187714 152187847 464_94996_58508(KMT2C)_33 0 — chr7 152194008 152194128 464_94995_58508(KMT2C)_32 0 — chr7 152194228 152194261 464_94994_58508(KMT2C)_31 0 — chr7 152194439 152194568 464_94993_58508(KMT2C)_30 0 — chr7 152195521 152195569 464_94992_58508(KMT2C)_29 0 — chr7 152195906 152196011 464_94991_58508(KMT2C)_28 0 — chr7 152199278 152199459 464_94990_58508(KMT2C)_27 0 — chr7 152202933 152203064 464_94989_58508(KMT2C)_26 0 — chr7 152205105 152205225 464_94988_58508(KMT2C)_25 0 — chr7 152207299 152207428 464_94987_58508(KMT2C)_24 0 — chr7 152220522 152220735 464_94986_58508(KMT2C)_23 0 — chr7 152222000 152222066 464_94985_58508(KMT2C)_22 0 — chr7 152222572 152222682 464_94984_58508(KMT2C)_21 0 — chr7 152224014 152224179 464_94983_58508(KMT2C)_20 0 — chr7 152224434 152224616 464_94982_58508(KMT2C)_19 0 — chr7 152229922 152230027 464_94981_58508(KMT2C)_18 0 — chr7 152230219 152230321 464_94980_58508(KMT2C)_17 0 — chr7 152235816 152235933 464_94979_58508(KMT2C)_16 0 — chr7 152238706 152238826 464_94978_58508(KMT2C)_15 0 — chr7 152247901 152248620 464_94977_58508(KMT2C)_14 0 — chr7 152249875 152249953 464_94976_58508(KMT2C)_13 0 — chr7 152250852 152250966 464_94975_58508(KMT2C)_12 0 — chr7 152251938 152252090 464_94974_58508(KMT2C)_11 0 — chr7 152252545 152252715 464_94973_58508(KMT2C)_10 0 — chr7 152263015 152263130 464_94972_58508(KMT2C)_9 0 — chr7 152265037 152265209 464_94971_58508(KMT2C)_8 0 — chr7 152273704 152273867 464_94970_58508(KMT2C)_7 0 — chr7 152309965 152310075 464_94969_58508(KMT2C)_6 0 — chr7 152311797 152311946 464_94968_58508(KMT2C)_5 0 — chr7 152315137 152315338 464_94967_58508(KMT2C)_4 0 — chr7 152330600 152330742 464_94966_58508(KMT2C)_3 0 — chr7 152358586 152358675 464_94965_58508(KMT2C)_2 0 — chr7 152435625 152435786 464_94964_58508(KMT2C)_1 0 — chr8 38413627 38413804 461_60334_2260(FGFR1)_21a 0 — chr8 38413917 38414023 461_60333_2260(FGFR1)_20a 0 — chr8 38414151 38414289 461_60332_2260(FGFR1)_19a 0 — chr8 38414558 38414629 461_60331_2260(FGFR1)_18a 0 — chr8 38414778 38414901 461_60330_2260(FGFR1)_17a 0 — chr8 38415869 38416060 461_60329_2260(FGFR1)_16a 0 — chr8 38417305 38417416 461_60328_2260(FGFR1)_15a 0 — chr8 38417869 38417991 461_60327_2260(FGFR1)_14a 0 — chr8 38418227 38418373 461_60326_2260(FGFR1)_13a 0 — chr8 38419532 38419735 461_60325_2260(FGFR1)_12a 0 — chr8 38421796 38421941 461_60324_2260(FGFR1)_11a 0 — chr8 38424508 38424699 461_60323_2260(FGFR1)_10a 0 — chr8 38426121 38426245 461_60322_2260(FGFR1)_9a 0 — chr8 38427920 38428093 461_60321_2260(FGFR1)_8a 0 — chr8 38428345 38428435 461_60320_2260(FGFR1)_7a 0 — chr8 38429681 38429948 461_60319_2260(FGFR1)_6a 0 — chr8 38440305 38440373 461_60318_2260(FGFR1)_5a 0 — chr8 38457355 38457534 461_60317_2260(FGFR1)_4a 0 — chr8 38461095 38461106 461_60316_2260(FGFR1)_3a 0 — chr9 5021987 5022213 463_81562_3717(JAK2)_3 0 — chr9 5029782 5029906 463_81563_3717(JAK2)_4 0 — chr9 5044402 5044520 463_81564_3717(JAK2)_5 0 — chr9 5050685 5050831 463_81648_3717(JAK2)_6 0 — chr9 5054562 5054884 463_81649_3717(JAK2)_7 0 — chr9 5055668 5055788 463_81650_3717(JAK2)_8 0 — chr9 5064882 5065040 463_81651_3717(JAK2)_9 0 — chr9 5066677 5066789 463_81652_3717(JAK2)_10 0 — chr9 5069021 5069208 463_81653_3717(JAK2)_11 0 — chr9 5069924 5070052 463_81654_3717(JAK2)_12 0 — chr9 5072491 5072626 463_81655_3717(JAK2)_13 0 — chr9 5073697 5073785 463_81656_3717(JAK2)_14 0 — chr9 5077452 5077580 463_81657_3717(JAK2)_15 0 — chr9 5078305 5078444 463_81658_3717(JAK2)_16 0 — chr9 5080228 5080380 463_81659_3717(JAK2)_17 0 — chr9 5080532 5080683 463_81660_3717(JAK2)_18 0 — chr9 5081724 5081861 463_81661_3717(JAK2)_19 0 — chr9 5089673 5089863 463_81662_3717(JAK2)_20 0 — chr9 5090445 5090570 463_81663_3717(JAK2)_21 0 — chr9 5090738 5090911 463_81664_3717(JAK2)_22 0 — chr9 5123003 5123121 463_81665_3717(JAK2)_23 0 — chr9 5126332 5126446 463_81666_3717(JAK2)_24 0 — chr9 5126683 5126791 463_81667_3717(JAK2)_25 0 — chr9 21968228 21968242 428_25768_1029(CDKN2A)_7a 0 — chr9 21968469 21968771 428_25767_1029(CDKN2A)_6a 0 — chr9 21970901 21971208 428_25766_1029(CDKN2A)_5a 0 — chr9 21971328 21971400 428_25765_1029(CDKN2A)_4a 0 — chr9 21974403 21975133 428_25764_1029(CDKN2A)_3a 0 — chr9 21991594 21992480 428_25763_1029(CDKN2A)_2a 0 — chr9 21994138 21994454 428_25762_1029(CDKN2A)_1a 0 — chr9 77721322 77721513 462_70181_2776(GNAQ)_7 0 — chr9 77728513 77728667 462_70180_2776(GNAQ)_6 0 — chr9 77794462 77794592 462_70179_2776(GNAQ)_5 0 — chr9 77797519 77797648 462_70178_2776(GNAQ)_4 0 — chr9 77815615 77815770 462_70177_2776(GNAQ)_3 0 — chr9 77922160 77922345 462_70176_2776(GNAQ)_2 0 — chr9 78031099 78031235 462_70175_2776(GNAQ)_1 0 — chr9 125236591 125237154 463_79198_3309(HSPA5)_8 0 — chr9 125238140 125238308 463_79197_3309(HSPA5)_7 0 — chr9 125238589 125238827 463_79196_3309(HSPA5)_6 0 — chr9 125238940 125239331 463_79195_3309(HSPA5)_5 0 — chr9 125239420 125239533 463_79194_3309(HSPA5)_4 0 — chr9 125240171 125240309 463_79193_3309(HSPA5)_3 0 — chr9 125240675 125240907 463_79192_3309(HSPA5)_2 0 — chr9 125241004 125241126 463_79191_3309(HSPA5)_1 0 — chr9 130714319 130714455 426_351_25(ABL1)_1 0 — chr9 130835443 130835525 426_352_25(ABL1)_2 0 — chr9 130854063 130854237 426_353_25(ABL1)_3 0 — chr9 130854800 130855096 426_354_25(ABL1)_4 0 — chr9 130862762 130863035 426_355_25(ABL1)_5 0 — chr9 130872128 130872213 426_356_25(ABL1)_6 0 — chr9 130872859 130873037 426_357_25(ABL1)_7 0 — chr9 130874867 130875052 426_358_25(ABL1)_8 0 — chr9 130878414 130878567 426_359_25(ABL1)_9 0 — chr9 130880067 130880157 426_360_25(ABL1)_10 0 — chr9 130880499 130880664 426_361_25(ABL1)_11 0 — chr9 130883968 130885683 426_362_25(ABL1)_12 0 — chr9 132896234 132896754 476_182337_7248(TSC1)_24 0 — chr9 132897183 132897345 476_182336_7248(TSC1)_23 0 — chr9 132897422 132897610 476_182335_7248(TSC1)_22 0 — chr9 132900714 132900837 476_182334_7248(TSC1)_21 0 — chr9 132901588 132901699 476_182333_7248(TSC1)_20 0 — chr9 132902604 132902787 476_182332_7248(TSC1)_19 0 — chr9 132903650 132903817 476_182331_7248(TSC1)_18 0 — chr9 132904410 132904454 476_182330_7248(TSC1)_17 0 — chr9 132905580 132906139 476_182329_7248(TSC1)_16 0 — chr9 132906730 132906835 476_182328_7248(TSC1)_15 0 — chr9 132907300 132907370 476_182327_7248(TSC1)_14 0 — chr9 132910570 132910692 476_182326_7248(TSC1)_13 0 — chr9 132911001 132911113 476_182325_7248(TSC1)_12 0 — chr9 132911452 132911568 476_182324_7248(TSC1)_11 0 — chr9 132912281 132912457 476_182323_7248(TSC1)_10 0 — chr9 132921362 132921436 476_182322_7248(TSC1)_9 0 — chr9 132921818 132921973 476_182321_7248(TSC1)_8 0 — chr9 132923347 132923492 476_182320_7248(TSC1)_7 0 — chr9 132925586 132925739 476_182319_7248(TSC1)_6 0 — chr9 132927200 132927304 476_182318_7248(TSC1)_5 0 — chr9 132928766 132928946 476_182317_7248(TSC1)_4 0 — chr9 136496070 136497558 469_119168_4851(NOTCH1)_34a 0 — chr9 136498898 136498996 469_119167_4851(NOTCH1)_33a 0 — chr9 136499111 136499259 469_119166_4851(NOTCH1)_32a 0 — chr9 136500551 136500847 469_119165_4851(NOTCH1)_31a 0 — chr9 136501747 136501913 469_119164_4851(NOTCH1)_30a 0 — chr9 136502000 136502088 469_119163_4851(NOTCH1)_29a 0 — chr9 136502271 136502488 469_119162_4851(NOTCH1)_28a 0 — chr9 136503181 136503330 469_119161_4851(NOTCH1)_27a 0 — chr9 136504672 136505104 469_119160_4851(NOTCH1)_26a 0 — chr9 136505309 136505881 469_119159_4851(NOTCH1)_25a 0 — chr9 136506526 136506639 469_119158_4851(NOTCH1)_24a 0 — chr9 136506715 136506973 469_119157_4851(NOTCH1)_23a 0 — chr9 136507304 136507437 469_119156_4851(NOTCH1)_22a 0 — chr9 136507954 136508139 469_119155_4851(NOTCH1)_21a 0 — chr9 136508231 136508385 469_119154_4851(NOTCH1)_20a 0 — chr9 136508869 136509071 469_119153_4851(NOTCH1)_19a 0 — chr9 136509732 136509961 469_119152_4851(NOTCH1)_18a 0 — chr9 136510652 136510805 469_119151_4851(NOTCH1)_17a 0 — chr9 136511151 136511271 469_119150_4851(NOTCH1)_16a 0 — chr9 136513020 136513134 469_119149_4851(NOTCH1)_15a 0 — chr9 136513391 136513537 469_119148_4851(NOTCH1)_14a 0 — chr9 136514509 136514702 469_119147_4851(NOTCH1)_13a 0 — chr9 136515289 136515400 469_119146_4851(NOTCH1)_12a 0 — chr9 136515482 136515716 469_119145_4851(NOTCH1)_11a 0 — chr9 136515980 136516094 469_119144_4851(NOTCH1)_10a 0 — chr9 136517271 136517385 469_119143_4851(NOTCH1)_9a 0 — chr9 136517751 136517937 469_119142_4851(NOTCH1)_8a 0 — chr9 136518136 136518292 469_119141_4851(NOTCH1)_7a 0 — chr9 136518590 136518824 469_119140_4851(NOTCH1)_6a 0 — chr9 136519442 136519565 469_119139_4851(NOTCH1)_5a 0 — chr9 136522849 136523188 469_119138_4851(NOTCH1)_4a 0 — chr9 136523716 136523979 469_119137_4851(NOTCH1)_3a 0 — chr9 136544023 136544102 469_119136_4851(NOTCH1)_2a 0 — chr9 136545725 136545786 469_119135_4851(NOTCH1)_1a 0 — chrX 31121832 31121930 431_46921_1756(DMD)_85 0 — chrX 31126641 31126673 431_46920_1756(DMD)_84 0 — chrX 31134101 31134194 431_46919_1756(DMD)_83 0 — chrX 31146290 31146414 431_46918_1756(DMD)_82 0 — chrX 31147274 31147518 431_46917_1756(DMD)_81 0 — chrX 31169442 31169601 431_46916_1756(DMD)_80 0 — chrX 31172347 31172413 431_46915_1756(DMD)_79 0 — chrX 31173538 31173604 431_46914_1756(DMD)_78 0 — chrX 31177931 31177970 431_46913_1756(DMD)_77 0 — chrX 31178194 31178805 431_46912_1756(DMD)_76 0 — chrX 31180369 31180481 431_46911_1756(DMD)_75 0 — chrX 31182737 31182904 431_46910_1756(DMD)_74 0 — chrX 31203960 31204118 431_46909_1756(DMD)_73 0 — chrX 31206581 31206667 431_46908_1756(DMD)_72 0 — chrX 31209497 31209699 431_46907_1756(DMD)_71 0 — chrX 31223046 31223121 431_46906_1756(DMD)_70 0 — chrX 31260954 31261016 431_46905_1756(DMD)_69 0 — chrX 31266809 31266907 431_46904_1756(DMD)_68 0 — chrX 31323597 31323658 431_46903_1756(DMD)_67 0 — chrX 31348555 31348634 431_46902_1756(DMD)_66 0 — chrX 31444480 31444627 431_46901_1756(DMD)_65 0 — chrX 31478105 31478374 431_46900_1756(DMD)_64 0 — chrX 31478982 31479103 431_46899_1756(DMD)_63 0 — chrX 31496787 31496944 431_46898_1756(DMD)_62 0 — chrX 31507280 31507453 431_46897_1756(DMD)_61 0 — chrX 31508207 31508298 431_46896_1756(DMD)_60 0 — chrX 31627672 31627862 431_46895_1756(DMD)_59 0 — chrX 31657989 31658144 431_46894_1756(DMD)_58 0 — chrX 31679374 31679586 431_46893_1756(DMD)_57 0 — chrX 31729630 31729748 431_46892_1756(DMD)_56 0 — chrX 31773959 31774192 431_46891_1756(DMD)_55 0 — chrX 31819974 31820083 431_46890_1756(DMD)_54 0 — chrX 31836717 31836819 431_46889_1756(DMD)_53 0 — chrX 31875187 31875373 431_46888_1756(DMD)_52 0 — chrX 31929595 31929745 431_46887_1756(DMD)_51 0 — chrX 31932079 31932227 431_46886_1756(DMD)_50 0 — chrX 31968338 31968514 431_46885_1756(DMD)_49 0 — chrX 32155370 32155469 431_46884_1756(DMD)_48 0 — chrX 32216915 32217063 431_46883_1756(DMD)_47 0 — chrX 32287528 32287701 431_46882_1756(DMD)_46 0 — chrX 32310081 32310276 431_46881_1756(DMD)_45 0 — chrX 32342099 32342282 431_46880_1756(DMD)_44 0 — chrX 32343133 32343286 431_46879_1756(DMD)_43 0 — chrX 32345942 32346080 431_46878_1756(DMD)_42 0 — chrX 32348405 32348528 431_46877_1756(DMD)_41 0 — chrX 32362787 32362958 431_46876_1756(DMD)_40 0 — chrX 32364581 32364710 431_46875_1756(DMD)_39 0 — chrX 32365019 32365199 431_46874_1756(DMD)_38 0 — chrX 32380509 32380680 431_46873_1756(DMD)_37 0 — chrX 32386309 32386465 431_46872_1756(DMD)_36 0 — chrX 32389500 32389674 431_46871_1756(DMD)_35 0 — chrX 32390070 32390181 431_46870_1756(DMD)_34 0 — chrX 32411751 32411913 431_46869_1756(DMD)_33 0 — chrX 32412018 32412254 431_46868_1756(DMD)_32 0 — chrX 32438240 32438390 431_46867_1756(DMD)_31 0 — chrX 32441179 32441314 431_46866_1756(DMD)_30 0 — chrX 32448455 32448638 431_46865_1756(DMD)_29 0 — chrX 32454661 32454832 431_46864_1756(DMD)_28 0 — chrX 32463438 32463594 431_46863_1756(DMD)_27 0 — chrX 32464585 32464699 431_46862_1756(DMD)_26 0 — chrX 32468497 32468710 431_46861_1756(DMD)_25 0 — chrX 32472163 32472309 431_46860_1756(DMD)_24 0 — chrX 32484918 32485099 431_46859_1756(DMD)_23 0 — chrX 32491276 32491518 431_46858_1756(DMD)_22 0 — chrX 32501754 32501842 431_46857_1756(DMD)_21 0 — chrX 32518007 32518131 431_46856_1756(DMD)_20 0 — chrX 32545158 32545334 431_46855_1756(DMD)_19 0 — chrX 32565701 32565881 431_46854_1756(DMD)_18 0 — chrX 32573529 32573637 431_46853_1756(DMD)_17 0 — chrX 32573744 32573846 431_46852_1756(DMD)_16 0 — chrX 32595756 32595876 431_46851_1756(DMD)_15 0 — chrX 32614302 32614453 431_46850_1756(DMD)_14 0 — chrX 32644131 32644313 431_46849_1756(DMD)_13 0 — chrX 32644963 32645152 431_46848_1756(DMD)_12 0 — chrX 32697869 32697998 431_46847_1756(DMD)_11 0 — chrX 32699111 32699293 431_46846_1756(DMD)_10 0 — chrX 32809492 32809611 431_46845_1756(DMD)_9 0 — chrX 32816467 32816640 431_46844_1756(DMD)_8 0 — chrX 32823294 32823387 431_46843_1756(DMD)_7 0 — chrX 32844782 32844860 431_46842_1756(DMD)_6 0 — chrX 32849727 32849820 431_46841_1756(DMD)_5 0 — chrX 33020138 33020200 431_46840_1756(DMD)_4 0 — chrX 33128062 33128428 431_46839_1756(DMD)_3 0 — chrX 33211281 33211556 431_46838_1756(DMD)_2 0 — chrX 33339258 33339265 431_46837_1756(DMD)_1 0 — chrX 47145446 47145516 472_141747_8241(RBM10)_1 0 — chrX 47147356 47147498 472_141748_8241(RBM10)_2 0 — chrX 47169314 47169498 472_141749_8241(RBM10)_3 0 — chrX 47171027 47171258 472_141750_8241(RBM10)_4 0 — chrX 47173127 47173197 472_141751_8241(RBM10)_5 0 — chrX 47175018 47175092 472_141752_8241(RBM10)_6 0 — chrX 47176499 47176586 472_141753_8241(RBM10)_7 0 — chrX 47179102 47179163 472_141754_8241(RBM10)_8 0 — chrX 47179318 47179495 472_141755_8241(RBM10)_9 0 — chrX 47179879 47180040 472_141756_8241(RBM10)_10 0 — chrX 47180211 47180309 472_141757_8241(RBM10)_11 0 — chrX 47180418 47180506 472_141758_8241(RBM10)_12 0 — chrX 47181214 47181401 472_141759_8241(RBM10)_13 0 — chrX 47181506 47181646 472_141760_8241(RBM10)_14 0 — chrX 47181748 47181866 472_141761_8241(RBM10)_15 0 — chrX 47181950 47182042 472_141762_8241(RBM10)_16 0 — chrX 47182161 47182326 472_141763_8241(RBM10)_17 0 — chrX 47185054 47185204 472_141764_8241(RBM10)_18 0 — chrX 47185301 47185367 472_141765_8241(RBM10)_19 0 — chrX 47185441 47185630 472_141766_8241(RBM10)_20 0 — chrX 47185715 47185790 472_141767_8241(RBM10)_21 0 — chrX 47186064 47186171 472_141768_8241(RBM10)_22 0 — chrX 47186257 47186387 472_141769_8241(RBM10)_23 0 — chrX 47186473 47186599 472_141770_8241(RBM10)_24 0 —

Supplementary Data 2

chr9 136496070 136497558 469_119168_4851(NOTCH1)_34a 0 — chr9 136499111 136499259 469_119166_4851(NOTCH1)_32a 0 — chr9 136500551 136500847 469_119165_4851(NOTCH1)_31a 0 — chr9 136501747 136501913 469_119164_4851(NOTCH1)_30a 0 — chr9 136502000 136502088 469_119163_4851(NOTCH1)_29a 0 — chr9 136502271 136502488 469_119162_4851(NOTCH1)_28a 0 — chr9 136503181 136503330 469_119161_4851(NOTCH1)_27a 0 — chr9 136504672 136505104 469_119160_4851(NOTCH1)_26a 0 — chr9 136506526 136506639 469_119158_4851(NOTCH1)_24a 0 — chr9 136506715 136506973 469_119157_4851(NOTCH1)_23a 0 — chr9 136507304 136507437 469_119156_4851(NOTCH1)_22a 0 — chr9 136507954 136508139 469_119155_4851(NOTCH1)_21a 0 — chr9 136508231 136508385 469_119154_4851(NOTCH1)_20a 0 — chr9 136508869 136509071 469_119153_4851(NOTCH1)_19a 0 — chr9 136509732 136509961 469_119152_4851(NOTCH1)_18a 0 — chr9 136511151 136511271 469_119150_4851(NOTCH1)_16a 0 — chr9 136513020 136513134 469_119149_4851(NOTCH1)_15a 0 — chr9 136513391 136513537 469_119148_4851(NOTCH1)_14a 0 — chr9 136514509 136514702 469_119147_4851(NOTCH1)_13a 0 — chr9 136515289 136515400 469_119146_4851(NOTCH1)_12a 0 — chr9 136515482 136515716 469_119145_4851(NOTCH1)_11a 0 — chr9 136515980 136516094 469_119144_4851(NOTCH1)_10a 0 — chr9 136517751 136517937 469_119142_4851(NOTCH1)_8a 0 — chr9 136518136 136518292 469_119141_4851(NOTCH1)_7a 0 — chr9 136518590 136518824 469_119140_4851(NOTCH1)_6a 0 — chr9 136519442 136519565 469_119139_4851(NOTCH1)_5a 0 — chr9 136522849 136523188 469_119138_4851(NOTCH1)_4a 0 — chr9 136523716 136523979 469_119137_4851(NOTCH1)_3a 0 — chr9 136544023 136544102 469_119136_4851(NOTCH1)_2a 0 — chr6 32195436 32196421 469_119235_4855(NOTCH4)_29 0 — chr6 32197298 32197594 469_119233_4855(NOTCH4)_27 0 — chr6 32198420 32198559 469_119232_4855(NOTCH4)_26 0 — chr6 32198648 32198730 469_119231_4855(NOTCH4)_25 0 — chr6 32198925 32199145 469_119230_4855(NOTCH4)_24 0 — chr6 32200830 32201006 469_119229_4855(NOTCH4)_23 0 — chr6 32201116 32201500 469_119228_4855(NOTCH4)_22 0 — chr6 32202075 32202599 469_119227_4855(NOTCH4)_21 0 — chr6 32204136 32204389 469_119225_4855(NOTCH4)_19 0 — chr6 32210751 32210936 469_119224_4855(NOTCH4)_18 0 — chr6 32212473 32212627 469_119223_4855(NOTCH4)_17 0 — chr6 32212823 32212911 469_119222_4855(NOTCH4)_16 0 — chr6 32213134 32213252 469_119221_4855(NOTCH4)_15 0 — chr6 32213687 32213840 469_119220_4855(NOTCH4)_14 0 — chr6 32214109 32214255 469_119219_4855(NOTCH4)_13 0 — chr6 32216944 32217067 469_119217_4855(NOTCH4)_11 0 — chr6 32217152 32217266 469_119216_4855(NOTCH4)_10 0 — chr6 32217994 32218108 469_119215_4855(NOTCH4)_9 0 — chr6 32219591 32219786 469_119214_4855(NOTCH4)_8 0 — chr6 32220128 32220284 469_119213_4855(NOTCH4)_7 0 — chr6 32220404 32220641 469_119212_4855(NOTCH4)_6 0 — chr6 32220755 32220878 469_119211_4855(NOTCH4)_5 0 — chr6 32222510 32222806 469_119209_4855(NOTCH4)_3 0 — chr6 32223004 32223086 469_119208_4855(NOTCH4)_2 0 — chr6 32223855 32223928 469_119207_4855(NOTCH4)_1 0 — chr5 171410526 171410565 469_119426_4869(NPM1)_12 0 — chr5 171407699 171407774 469_119425_4869(NPM1)_11 0 — chr5 171406396 171406734 469_119424_4869(NPM1)_10 0 — chr5 171405301 171405403 469_119423_4869(NPM1)_9 0 — chr5 171400838 171400925 469_119422_4869(NPM1)_8 0 — chr5 171392913 171392978 469_119420_4869(NPM1)_6 0 — chr5 171392709 171392816 469_119419_4869(NPM1)_5 0 — chr5 171391705 171391799 469_119418_4869(NPM1)_4 0 — chr5 171391304 171391424 469_119417_4869(NPM1)_3 0 — chr5 171390050 171390130 469_119416_4869(NPM1)_2 0 — chr5 171387948 171388006 469_119415_4869(NPM1)_1 0 — chr1 114708534 114708654 469_119576_4893(NRAS)_5 0 — chr1 114709568 114709728 469_119575_4893(NRAS)_4 0 — chr1 114713799 114713978 469_119574_4893(NRAS)_3 0 — chr1 114716049 114716160 469_119573_4893(NRAS)_2 0 — chr17 7669608 7669690 476_181712_7157(TP53)_11 0 — chr17 7670608 7670715 476_181711_7157(TP53)_10 0 — chr17 7673206 7673339 476_181710_7157(TP53)_9 0 — chr17 7673700 7673837 476_181708_7157(TP53)_7 0 — chr17 7674180 7674290 476_181707_7157(TP53)_6 0 — chr17 7674858 7674971 476_181706_7157(TP53)_5 0 — chr17 7675052 7675493 476_181705_7157(TP53)_4 0 — chr17 7675993 7676272 476_181704_7157(TP53)_3 0 — chr17 7676381 7676594 476_181703_7157(TP53)_2 0 — chr17 31349119 31349251 469_118622_4763(NF1)_49a 0 — chr17 31343008 31343135 469_118621_4763(NF1)_48a 0 — chr17 31340504 31340645 469_118620_4763(NF1)_47a 0 — chr17 31338024 31338139 469_118618_4763(NF1)_45a 0 — chr17 31337818 31337880 469_118617_4763(NF1)_44a 0 — chr17 31337367 31337582 469_118616_4763(NF1)_43a 0 — chr17 31336634 31336914 469_118615_4763(NF1)_42a 0 — chr17 31336332 31336473 469_118614_4763(NF1)_41a 0 — chr17 31334837 31335031 469_118613_4763(NF1)_40a 0 — chr17 31327498 31327839 469_118611_4763(NF1)_38a 0 — chr17 31325819 31326252 469_118610_4763(NF1)_37a 0 — chr17 31265228 31265339 469_118609_4763(NF1)_36a 0 — chr17 31261710 31261857 469_118608_4763(NF1)_35a 0 — chr17 31260368 31260515 469_118607_4763(NF1)_34a 0 — chr17 31259031 31259129 469_118606_4763(NF1)_33a 0 — chr17 31258343 31258502 469_118605_4763(NF1)_32a 0 — chr17 31248983 31249119 469_118603_4763(NF1)_30a 0 — chr17 31235917 31236021 469_118602_4763(NF1)_29a 0 — chr17 31235610 31235772 469_118601_4763(NF1)_28a 0 — chr17 31233001 31233213 469_118600_4763(NF1)_27a 0 — chr17 31232699 31232881 469_118599_4763(NF1)_26a 0 — chr17 31232072 31232189 469_118598_4763(NF1)_25a 0 — chr17 31230259 31230382 469_118596_4763(NF1)_23a 0 — chr17 31229834 31229974 469_118595_4763(NF1)_22a 0 — chr17 31229024 31229465 469_118594_4763(NF1)_21a 0 — chr17 31227522 31227606 469_118593_4763(NF1)_20a 0 — chr17 31227217 31227291 469_118592_4763(NF1)_19a 0 — chr17 31226434 31226684 469_118591_4763(NF1)_18a 0 — chr17 31223443 31223567 469_118589_4763(NF1)_16a 0 — chr17 31221849 31222764 469_118588_4763(NF1)_15a 0 — chr17 31219004 31219118 469_118587_4763(NF1)_14a 0 — chr17 31214450 31214585 469_118586_4763(NF1)_13a 0 — chr17 31206239 31206371 469_118585_4763(NF1)_12a 0 — chr17 31201410 31201485 469_118584_4763(NF1)_11a 0 — chr17 31200421 31200595 469_118582_4763(NF1)_9a 0 — chr17 31182507 31182665 469_118581_4763(NF1)_8a 0 — chr17 31181709 31181785 469_118580_4763(NF1)_7a 0 — chr17 31181421 31181489 469_118579_4763(NF1)_6a 0 — chr17 31169890 31169997 469_118578_4763(NF1)_5a 0 — chr17 31163185 31163376 469_118577_4763(NF1)_4a 0 — chr17 31155982 31156126 469_118575_4763(NF1)_2a 0 — chr17 31095309 31095369 469_118574_4763(NF1)_1a 0 — chr17 31367224 31367278 469_118632_4763(NF1)_59a 0 — chr17 31362287 31362364 469_118631_4763(NF1)_58a 0 — chr17 31360486 31360703 469_118630_4763(NF1)_57a 0 — chr17 31358968 31359015 469_118629_4763(NF1)_56a 0 — chr17 31358479 31358622 469_118628_4763(NF1)_55a 0 — chr17 31357268 31357369 469_118627_4763(NF1)_54a 0 — chr9 136498898 136498996 469_119167_4851(NOTCH1)_33a 0 — chr9 136505309 136505881 469_119159_4851(NOTCH1)_25a 0 — chr9 136510652 136510805 469_119151_4851(NOTCH1)_17a 0 — chr9 136517271 136517385 469_119143_4851(NOTCH1)_9a 0 — chr9 136545725 136545786 469_119135_4851(NOTCH1)_1a 0 — chr6 32196924 32197072 469_119234_4855(NOTCH4)_28 0 — chr6 32203769 32203882 469_119226_4855(NOTCH4)_20 0 — chr6 32215225 32215385 469_119218_4855(NOTCH4)_12 0 — chr6 32220977 32221325 469_119210_4855(NOTCH4)_4 0 — chr3 179234093 179234364 470_127823_5290(PIK3CA)_21 0 — chr3 179230003 179230121 470_127821_5290(PIK3CA)_19 0 — chr3 179229271 179229442 470_127820_5290(PIK3CA)_18 0 — chr3 179225961 179226040 470_127819_5290(PIK3CA)_17 0 — chr3 179224699 179224821 470_127818_5290(PIK3CA)_16 0 — chr3 179224080 179224187 470_127817_5290(PIK3CA)_15 0 — chr3 179220985 179221157 470_127816_5290(PIK3CA)_14 0 — chr3 179219570 179219735 470_127814_5290(PIK3CA)_12 0 — chr3 179219195 179219277 470_127813_5290(PIK3CA)_11 0 — chr3 179218209 179218334 470_127812_5290(PIK3CA)_10 0 — chr3 179210430 179210565 470_127811_5290(PIK3CA)_9 0 — chr3 179210185 179210338 470_127810_5290(PIK3CA)_8 0 — chr3 179209594 179209700 470_127809_5290(PIK3CA)_7 0 — chr3 179204502 179204588 470_127808_5290(PIK3CA)_6 0 — chr3 179201289 179201540 470_127806_5290(PIK3CA)_4 0 — chr3 179199689 179199899 470_127805_5290(PIK3CA)_3 0 — chr3 179198825 179199177 470_127804_5290(PIK3CA)_2 0 — chr3 179230224 179230376 470_127822_5290(PIK3CA)_20 0 — chr3 179219948 179220052 470_127815_5290(PIK3CA)_13 0 — chr3 179203543 179203789 470_127807_5290(PIK3CA)_5 0 — chr5 68297411 68297601 470_127791_5295(PIK3R1)_19 0 — chr5 68296170 68296341 470_127790_5295(PIK3R1)_18 0 — chr5 68295419 68295488 470_127789_5295(PIK3R1)_17 0 — chr5 68295147 68295324 470_127788_5295(PIK3R1)_16 0 — chr5 68293708 68293834 470_127786_5295(PIK3R1)_14 0 — chr5 68293302 68293483 470_127785_5295(PIK3R1)_13 0 — chr5 68293100 68293199 470_127784_5295(PIK3R1)_12 0 — chr5 68292567 68292729 470_127783_5295(PIK3R1)_11 0 — chr5 68292258 68292361 470_127782_5295(PIK3R1)_10 0 — chr5 68290638 68290834 470_127781_5295(PIK3R1)_9 0 — chr5 68280926 68281006 470_127779_5295(PIK3R1)_7 0 — chr5 68280527 68280729 470_127778_5295(PIK3R1)_6 0 — chr5 68279601 68279733 470_127777_5295(PIK3R1)_5 0 — chr5 68273938 68274013 470_127776_5295(PIK3R1)_4 0 — chr5 68273389 68273482 470_127775_5295(PIK3R1)_3 0 — chr5 68226675 68227009 470_127774_5295(PIK3R1)_2 0 — chr5 68294535 68294678 470_127787_5295(PIK3R1)_15 0 — chr5 68288423 68288751 470_127780_5295(PIK3R1)_8 0 — chr10 43124882 43124982 473_148936_5979(RET)_18a 0 — chr10 43114479 43114736 473_148929_5979(RET)_11a 0 — chr10 43104951 43105193 473_148922_5979(RET)_4a 0 — chr17 58363525 58363600 473_154856_54894(RNF43)_4 0 — chr17 7673534 7673608 476_181709_7157(TP53)_8 0 — chr9 132896234 132896754 476_182337_7248(TSC1)_24 0 — chr9 132897183 132897345 476_182336_7248(TSC1)_23 0 — chr9 132897422 132897610 476_182335_7248(TSC1)_22 0 — chr9 132900714 132900837 476_182334_7248(TSC1)_21 0 — chr9 132901588 132901699 476_182333_7248(TSC1)_20 0 — chr9 132902604 132902787 476_182332_7248(TSC1)_19 0 — chr9 132903650 132903817 476_182331_7248(TSC1)_18 0 — chr9 132905580 132906139 476_182329_7248(TSC1)_16 0 — chr9 132906730 132906835 476_182328_7248(TSC1)_15 0 — chr9 132907300 132907370 476_182327_7248(TSC1)_14 0 — chr9 132910570 132910692 476_182326_7248(TSC1)_13 0 — chr9 132911001 132911113 476_182325_7248(TSC1)_12 0 — chr9 132911452 132911568 476_182324_7248(TSC1)_11 0 — chr9 132912281 132912457 476_182323_7248(TSC1)_10 0 — chr9 132921818 132921973 476_182321_7248(TSC1)_8 0 — chr9 132923347 132923492 476_182320_7248(TSC1)_7 0 — chr9 132925586 132925739 476_182319_7248(TSC1)_6 0 — chr9 132927200 132927304 476_182318_7248(TSC1)_5 0 — chr9 132928766 132928946 476_182317_7248(TSC1)_4 0 — chr9 132921362 132921436 476_182322_7248(TSC1)_9 0 — chr9 132904410 132904454 476_182330_7248(TSC1)_17 0 — chr16 2058746 2058873 476_182347_7249(TSC2)_10 0 — chr16 2057104 2057178 476_182346_7249(TSC2)_9 0 — chr16 2056195 2056244 476_182344_7249(TSC2)_7 0 — chr16 2055401 2055519 476_182343_7249(TSC2)_6 0 — chr16 2054295 2054440 476_182342_7249(TSC2)_5 0 — chr16 2053341 2053452 476_182341_7249(TSC2)_4 0 — chr16 2050399 2050486 476_182340_7249(TSC2)_3 0 — chr16 2048586 2048753 476_182339_7249(TSC2)_2 0 — chr16 2086192 2086379 476_182374_7249(TSC2)_37 0 — chr16 2080164 2080377 476_182367_7249(TSC2)_30 0 — chr16 2075798 2075892 476_182360_7249(TSC2)_23 0 — chr16 2065518 2065635 476_182353_7249(TSC2)_16 0 — chr16 2056643 2056769 476_182345_7249(TSC2)_8 0 — chr16 2047821 2048065 476_182338_7249(TSC2)_1 0 — chr3 37050485 37050653 466_106476_4292(MLH1)_21 0 — chr3 37048516 37048609 466_106474_4292(MLH1)_19 0 — chr3 37047518 37047683 466_106473_4292(MLH1)_18 0 — chr3 37042267 37042331 466_106472_4292(MLH1)_17 0 — chr3 37040185 37040294 466_106471_4292(MLH1)_16 0 — chr3 37028783 37028932 466_106470_4292(MLH1)_15 0 — chr3 37025636 37026007 466_106469_4292(MLH1)_14 0 — chr3 37020309 37020463 466_106468_4292(MLH1)_13 0 — chr3 37014431 37014544 466_106466_4292(MLH1)_11 0 — chr3 37012010 37012099 466_106465_4292(MLH1)_10 0 — chr3 37011819 37011862 466_106464_4292(MLH1)_9 0 — chr17 31374012 31374155 469_118633_4763(NF1)_60a 0 — chr17 31356959 31357090 469_118626_4763(NF1)_53a 0 — chr17 31338703 31338805 469_118619_4763(NF1)_46a 0 — chr17 31330295 31330498 469_118612_4763(NF1)_39a 0 — chr17 31252937 31253000 469_118604_4763(NF1)_31a 0 — chr17 31230841 31230925 469_118597_4763(NF1)_24a 0 — chr17 31225094 31225250 469_118590_4763(NF1)_17a 0 — chr17 31201036 31201159 469_118583_4763(NF1)_10a 0 — chr17 31159009 31159093 469_118576_4763(NF1)_3a 0 — chr7 116695756 116695799 466_106278_4233(MET)_2a 0 — chr7 116699070 116700284 466_106279_4233(MET)_3a 0 — chr7 116724099 116724164 466_106280_4233(MET)_4a 0 — chr7 116724771 116724847 466_106281_4233(MET)_5a 0 — chr7 116731667 116731859 466_106282_4233(MET)_6a 0 — chr7 116739949 116740084 466_106283_4233(MET)_7a 0 — chr7 116755354 116755515 466_106285_4233(MET)_9a 0 — chr7 116757436 116757539 466_106286_4233(MET)_10a 0 — chr7 116757637 116757774 466_106287_4233(MET)_11a 0 — chr7 116758458 116758620 466_106288_4233(MET)_12a 0 — chr7 116759336 116759490 466_106289_4233(MET)_13a 0 — chr7 116763049 116763268 466_106290_4233(MET)_14a 0 — chr7 116771497 116771654 466_106292_4233(MET)_16a 0 — chr7 116771848 116771989 466_106293_4233(MET)_17a 0 — chr7 116774880 116775111 466_106294_4233(MET)_18a 0 — chr7 116777388 116777469 466_106295_4233(MET)_19a 0 — chr7 116778775 116778957 466_106296_4233(MET)_20a 0 — chr7 116781987 116782097 466_106297_4233(MET)_21a 0 — chr7 116783303 116783469 466_106298_4233(MET)_22a 0 — chr7 116795886 116796124 466_106300_4233(MET)_24a 0 — chr1 204525327 204525346 466_106137_4194(MDM4)_2a 0 — chr1 204542783 204542944 466_106144_4194(MDM4)_9a 0 — chr1 204525483 204525596 466_106138_4194(MDM4)_3a 0 — chr1 204526359 204526434 466_106139_4194(MDM4)_4a 0 — chr1 204530683 204530817 466_106140_4194(MDM4)_5a 0 — chr1 204532190 204532246 466_106141_4194(MDM4)_6a 0 — chr1 204537429 204537497 466_106142_4194(MDM4)_7a 0 — chr1 204538208 204538308 466_106143_4194(MDM4)_8a 0 — chr1 204544534 204544684 466_106145_4194(MDM4)_10a 0 — chr1 204546796 204546877 466_106146_4194(MDM4)_11a 0 — chr1 204549112 204549682 466_106147_4194(MDM4)_12a 0 — chr12 68808949 68809086 466_106044_4193(MDM2)_2 0 — chr12 68828770 68828931 466_106051_4193(MDM2)_9 0 — chr12 68808477 68808491 466_106043_4193(MDM2)_1 0 — chr12 68809207 68809292 466_106045_4193(MDM2)_3 0 — chr12 68813553 68813628 466_106046_4193(MDM2)_4 0 — chr12 68816811 68816945 466_106047_4193(MDM2)_5 0 — chr12 68820324 68820374 466_106048_4193(MDM2)_6 0 — chr12 68824362 68824430 466_106049_4193(MDM2)_7 0 — chr12 68824554 68824651 466_106050_4193(MDM2)_8 0 — chr12 68835828 68835984 466_106052_4193(MDM2)_10 0 — chr12 68836671 68836749 466_106053_4193(MDM2)_11 0 — chr12 68839273 68839849 466_106054_4193(MDM2)_12 0 — chr4 55125226 55125293 464_88696_3791(KDR)_1a 0 — chr4 55110402 55110566 464_88704_3791(KDR)_9a 0 — chr4 55098136 55098272 464_88712_3791(KDR)_17a 0 — chr4 55089373 55089473 464_88720_3791(KDR)_25a 0 — chr5 171400152 171400210 469_119421_4869(NPM1)_7 0 — chr4 54285840 54285963 470_126855_5156(PDGFRA)_20a 0 — chr4 54285370 54285486 470_126854_5156(PDGFRA)_19a 0 — chr4 54280315 54280482 470_126852_5156(PDGFRA)_17a 0 — chr4 54278361 54278515 470_126851_5156(PDGFRA)_16a 0 — chr4 54277895 54278006 470_126850_5156(PDGFRA)_15a 0 — chr4 54277387 54277492 470_126849_5156(PDGFRA)_14a 0 — chr4 54274840 54274973 470_126848_5156(PDGFRA)_13a 0 — chr4 54274530 54274625 470_126847_5156(PDGFRA)_12a 0 — chr4 54273536 54273730 470_126846_5156(PDGFRA)_11a 0 — chr4 54270632 54270748 470_126844_5156(PDGFRA)_9a 0 — chr4 54267551 54267741 470_126843_5156(PDGFRA)_8a 0 — chr4 54267288 54267460 470_126842_5156(PDGFRA)_7a 0 — chr4 54264918 54265049 470_126841_5156(PDGFRA)_6a 0 — chr4 54263666 54263927 470_126840_5156(PDGFRA)_5a 0 — chr4 54261094 54261412 470_126839_5156(PDGFRA)_4a 0 — chr4 54295124 54295272 470_126860_5156(PDGFRA)_25a 0 — chr4 54289008 54289114 470_126858_5156(PDGFRA)_23a 0 — chr4 54288798 54288898 470_126857_5156(PDGFRA)_22a 0 — chr4 54287429 54287541 470_126856_5156(PDGFRA)_21a 0 — chr4 54290312 54290554 470_126859_5156(PDGFRA)_24a 0 — chr4 54281580 54281978 470_126853_5156(PDGFRA)_18a 0 — chr4 54272393 54272520 470_126845_5156(PDGFRA)_10a 0 — chr4 54258768 54258817 470_126838_5156(PDGFRA)_3a 0 — chr7 129210964 129211113 474_160573_6608(SMO)_10a 0 — chr7 129205202 129205412 474_160566_6608(SMO)_3a 0 — chr3 10149786 10150367 477_191810_7428(VHL)_3 0 — chr3 10146513 10146636 477_191809_7428(VHL)_2 0 — chr3 10141847 10142187 477_191808_7428(VHL)_1 0 — chr7 116769644 116769791 466_106291_4233(MET)_15a 0 — chr7 116740851 116741025 466_106284_4233(MET)_8a 0 — chr3 37008813 37008905 466_106463_4292(MLH1)_8 0 — chr3 37006990 37007063 466_106462_4292(MLH1)_7 0 — chr3 37004400 37004474 466_106461_4292(MLH1)_6 0 — chr3 36997155 36997300 466_106459_4292(MLH1)_4 0 — chr3 36996618 36996709 466_106458_4292(MLH1)_3 0 — chr3 36993768 36993890 466_106457_4292(MLH1)_2 0 — chr3 36993547 36993663 466_106456_4292(MLH1)_1 0 — chr3 37048903 37049017 466_106475_4292(MLH1)_20 0 — chr3 37017505 37017599 466_106467_4292(MLH1)_12 0 — chr3 37000954 37001053 466_106460_4292(MLH1)_5 0 — chr1 43352517 43352772 466_106809_4352(MPL)_12a 0 — chr1 43352215 43352303 466_106808_4352(MPL)_11a 0 — chr1 43348842 43349002 466_106806_4352(MPL)_9a 0 — chr1 43346791 43346934 466_106805_4352(MPL)_8a 0 — chr1 43346444 43346629 466_106804_4352(MPL)_7a 0 — chr1 43340386 43340513 466_106803_4352(MPL)_6a 0 — chr1 43339963 43340126 466_106802_4352(MPL)_5a 0 — chr1 43339270 43339569 466_106801_4352(MPL)_4a 0 — chr1 43338098 43338231 466_106799_4352(MPL)_2a 0 — chr1 43337848 43337927 466_106798_4352(MPL)_1a 0 — chr1 43349262 43349359 466_106807_4352(MPL)_10a 0 — chr1 43338541 43338720 466_106800_4352(MPL)_3a 0 — chr9 5029782 5029906 463_81563_3717(JAK2)_4 0 — chr9 5054562 5054884 463_81649_3717(JAK2)_7 0 — chr9 5073697 5073785 463_81656_3717(JAK2)_14 0 — chr9 5090738 5090911 463_81664_3717(JAK2)_22 0 — chr9 5021987 5022213 463_81562_3717(JAK2)_3 0 — chr9 5044402 5044520 463_81564_3717(JAK2)_5 0 — chr1 64883276 64883475 463_81625_3716(JAK1)_4a 0 — chr1 64855508 64855698 463_81633_3716(JAK1)_12a 0 — chr1 64841450 64841601 463_81640_3716(JAK1)_19a 0 — chr1 64844063 64844215 463_81639_3716(JAK1)_18a 0 — chr1 64841244 64841339 463_81641_3716(JAK1)_20a 0 — chr7 116795654 116795791 466_106299_4233(MET)_23a 0 — chr1 64839602 64839795 463_81642_3716(JAK1)_21a 0 — chr4 55115280 55115411 464_88699_3791(KDR)_4a 0 — chr4 55114873 55115042 464_88700_3791(KDR)_5a 0 — chr4 55114125 55114265 464_88701_3791(KDR)_6a 0 — chr4 55113303 55113481 464_88702_3791(KDR)_7a 0 — chr4 55110653 55110768 464_88703_3791(KDR)_8a 0 — chr4 55107736 55107893 464_88705_3791(KDR)_10a 0 — chr4 55106686 55106810 464_88706_3791(KDR)_11a 0 — chr4 55105831 55105940 464_88707_3791(KDR)_12a 0 — chr4 55104642 55104984 464_88708_3791(KDR)_13a 0 — chr4 55102361 55102508 464_88709_3791(KDR)_14a 0 — chr4 55101896 55102028 464_88710_3791(KDR)_15a 0 — chr4 55098696 55098803 464_88711_3791(KDR)_16a 0 — chr4 55097661 55097766 464_88713_3791(KDR)_18a 0 — chr4 55096228 55096342 464_88714_3791(KDR)_19a 0 — chr4 55095576 55095665 464_88715_3791(KDR)_20a 0 — chr4 55094801 55094955 464_88716_3791(KDR)_21a 0 — chr4 55092616 55092714 464_88717_3791(KDR)_22a 0 — chr4 55089955 55090078 464_88718_3791(KDR)_23a 0 — chr4 55089690 55089802 464_88719_3791(KDR)_24a 0 — chr12 120988832 120989032 463_81839_6927(HNF1A)_2 0 — chr12 120993519 120993706 463_81840_6927(HNF1A)_3 0 — chr12 120994163 120994405 463_81841_6927(HNF1A)_4 0 — chr12 120996261 120996413 463_81842_6927(HNF1A)_5 0 — chr12 120996540 120997166 463_81843_6927(HNF1A)_6 0 — chr22 23793558 23793688 474_160330_6598(SMARCB)_3 0 — chr4 55088867 55088973 464_88721_3791(KDR)_26a 0 — chr4 55087606 55087758 464_88722_3791(KDR)_27a 0 — chr4 55082535 55082635 464_88723_3791(KDR)_28a 0 — chr4 55081955 55082041 464_88724_3791(KDR)_29a 0 — chr4 55079940 55080163 464_88725_3791(KDR)_30a 0 — chr12 120997473 120997665 463_81844_6927(HNF1A)_7 0 — chr12 121001064 121001192 463_81846_6927(HNF1A)_9 0 — chr16 2088445 2088610 476_182379_7249(TSC2)_42 0 — chr16 2088226 2088325 476_182378_7249(TSC2)_41 0 — chr16 2088047 2088139 476_182377_7249(TSC2)_40 0 — chr16 2087862 2087941 476_182376_7249(TSC2)_39 0 — chr16 2086731 2086871 476_182375_7249(TSC2)_38 0 — chr16 2085229 2085322 476_182373_7249(TSC2)_36 0 — chr16 2084950 2085026 476_182372_7249(TSC2)_35 0 — chr16 2084227 2084715 476_182371_7249(TSC2)_34 0 — chr16 2083694 2083816 476_182370_7249(TSC2)_33 0 — chr16 2082435 2082504 476_182369_7249(TSC2)_32 0 — chr16 2081594 2081798 476_182368_7249(TSC2)_31 0 — chr16 2079556 2079669 476_182366_7249(TSC2)_29 0 — chr16 2079275 2079428 476_182365_7249(TSC2)_28 0 — chr16 2079031 2079196 476_182364_7249(TSC2)_27 0 — chr16 2077597 2077726 476_182363_7249(TSC2)_26 0 — chr16 2076490 2076585 476_182362_7249(TSC2)_25 0 — chr16 2076067 2076257 476_182361_7249(TSC2)_24 0 — chr16 2074199 2074389 476_182359_7249(TSC2)_22 0 — chr16 2072848 2072983 476_182358_7249(TSC2)_21 0 — chr16 2072240 2072363 476_182357_7249(TSC2)_20 0 — chr16 2071783 2071934 476_182356_7249(TSC2)_19 0 — chr16 2071509 2071616 476_182355_7249(TSC2)_18 0 — chr16 2070455 2070578 476_182354_7249(TSC2)_17 0 — chr16 2064271 2064427 476_182352_7249(TSC2)_15 0 — chr16 2062971 2063053 476_182351_7249(TSC2)_14 0 — chr16 2062496 2062600 476_182350_7249(TSC2)_13 0 — chr16 2061870 2062008 476_182349_7249(TSC2)_12 0 — chr16 2060669 2060813 476_182348_7249(TSC2)_11 0 — chr4 55121096 55121190 464_88697_3791(KDR)_2a 0 — chr4 55118603 55118800 464_88698_3791(KDR)_3a 0 — chr15 90088358 90088502 463_79505_3418(IDH2)_6a 0 — chr15 90087438 90087575 463_79506_3418(IDH2)_7a 0 — chr15 90087111 90087263 463_79507_3418(IDH2)_8a 0 — chr15 90085274 90085387 463_79508_3418(IDH2)_9a 0 — chr15 90085000 90085098 463_79509_3418(IDH2)_10a 0 — chr15 90084265 90084353 463_79511_3418(IDH2)_12a 0 — chr15 90102275 90102390 463_79500_3418(IDH2)_1a 0 — chr15 90100575 90100690 463_79501_3418(IDH2)_2a 0 — chr15 90091552 90091644 463_79502_3418(IDH2)_3a 0 — chr15 90090478 90090644 463_79503_3418(IDH2)_4a 0 — chr2 208251429 208251551 463_79492_3417(IDH1)_6a 0 — chr2 208248368 208248660 463_79493_3417(IDH1)_7a 0 — chr2 208245318 208245424 463_79494_3417(IDH1)_8a 0 — chr2 208243426 208243604 463_79495_3417(IDH1)_9a 0 — chr2 208239862 208240003 463_79497_3417(IDH1)_11a 0 — chr2 208239070 208239233 463_79498_3417(IDH1)_12a 0 — chr2 208237078 208237169 463_79499_3417(IDH1)_13a 0 — chr11 533765 533944 463_79035_3265(HRAS)_3a 0 — chr11 533452 533612 463_79036_3265(HRAS)_4a 0 — chr11 533276 533358 463_79037_3265(HRAS)_5a 0 — chr11 532588 532755 463_79038_3265(HRAS)_6a 0 — chr10 43112852 43112963 473_148927_5979(RET)_9a 0 — chr10 43112098 43112224 473_148926_5979(RET)_8a 0 — chr10 8055655 8055896 462_69261_2625(GATA3)_4a 0 — chr10 8058304 8058841 462_69262_2625(GATA3)_5a 0 — chr10 8063992 8064138 462_69263_2625(GATA3)_6a 0 — chr10 8069472 8069598 462_69264_2625(GATA3)_7a 0 — chr10 8073738 8074023 462_69265_2625(GATA3)_8a 0 — chr19 17844233 17844430 463_81744_3718(JAK3)_2a 0 — chr19 17843776 17843900 463_81745_3718(JAK3)_3a 0 — chr19 17843379 17843491 463_81746_3718(JAK3)_4a 0 — chr19 17843026 17843172 463_81747_3718(JAK3)_5a 0 — chr19 17842315 17842610 463_81748_3718(JAK3)_6a 0 — chr19 17841639 17841762 463_81749_3718(JAK3)_7a 0 — chr19 17840229 17840341 463_81751_3718(JAK3)_9a 0 — chr19 17839476 17839663 463_81752_3718(JAK3)_10a 0 — chr19 17838262 17838390 463_81753_3718(JAK3)_11a 0 — chr19 17837931 17838063 463_81754_3718(JAK3)_12a 0 — chr19 17837128 17837213 463_81755_3718(JAK3)_13a 0 — chr19 17835923 17836051 463_81756_3718(JAK3)_14a 0 — chr19 17835082 17835215 463_81757_3718(JAK3)_15a 0 — chr19 17834570 17834721 463_81759_3718(JAK3)_17a 0 — chr19 17832789 17832929 463_81760_3718(JAK3)_18a 0 — chr19 17832518 17832708 463_81761_3718(JAK3)_19a 0 — chr19 17831673 17831798 463_81762_3718(JAK3)_20a 0 — chr19 17831227 17831400 463_81763_3718(JAK3)_21a 0 — chr19 17830502 17830620 463_81764_3718(JAK3)_22a 0 — chr19 17830107 17830218 463_81765_3718(JAK3)_23a 0 — chr4 152350041 152350124 461_64086_55294(FBXW7)_7 0 — chr4 152324183 152324394 461_64095_55294(FBXW7)_16 0 — chr10 43128111 43128269 473_148938_5979(RET)_20a 0 — chr10 43126574 43127504 473_148937_5979(RET)_19a 0 — chr10 43123670 43123808 473_148935_5979(RET)_17a 0 — chr10 43121945 43122016 473_148934_5979(RET)_16a 0 — chr10 43120080 43120203 473_148933_5979(RET)_15a 0 — chr10 43119530 43119745 473_148932_5979(RET)_14a 0 — chr10 43118372 43118480 473_148931_5979(RET)_13a 0 — chr10 43116583 43116731 473_148930_5979(RET)_12a 0 — chr10 43113555 43113675 473_148928_5979(RET)_10a 0 — chr19 17847945 17848061 463_81743_3718(JAK3)_1a 0 — chr13 48477354 48477404 472_141468_5925(RB1)_26a 0 — chr13 48476700 48476843 472_141467_5925(RB1)_25a 0 — chr13 48473359 48473390 472_141466_5925(RB1)_24a 0 — chr13 48465204 48465368 472_141465_5925(RB1)_23a 0 — chr13 48464997 48465111 472_141464_5925(RB1)_22a 0 — chr13 48463730 48463835 472_141463_5925(RB1)_21a 0 — chr13 48456203 48456349 472_141461_5925(RB1)_19a 0 — chr13 48452992 48453111 472_141460_5925(RB1)_18a 0 — chr13 48381246 48381443 472_141459_5925(RB1)_17a 0 — chr13 48380164 48380241 472_141458_5925(RB1)_16a 0 — chr13 48380052 48380084 472_141457_5925(RB1)_15a 0 — chr13 48379593 48379650 472_141456_5925(RB1)_14a 0 — chr13 48376917 48377034 472_141455_5925(RB1)_13a 0 — chr13 48368526 48368604 472_141453_5925(RB1)_11a 0 — chr13 48367493 48367603 472_141452_5925(RB1)_10a 0 — chr13 48364893 48364971 472_141451_5925(RB1)_9a 0 — chr13 48362814 48362957 472_141450_5925(RB1)_8a 0 — chr13 48360016 48360127 472_141449_5925(RB1)_7a 0 — chr13 48348955 48349023 472_141448_5925(RB1)_6a 0 — chr13 48345079 48345199 472_141446_5925(RB1)_4a 0 — chr13 48342598 48342714 472_141445_5925(RB1)_3a 0 — chr13 48307279 48307406 472_141444_5925(RB1)_2a 0 — chr13 48303912 48304049 472_141443_5925(RB1)_1a 0 — chr4 152411159 152411872 461_64083_55294(FBXW7)_4 0 — chr4 152382188 152382512 461_64084_55294(FBXW7)_5 0 — chr4 152352469 152352958 461_64085_55294(FBXW7)6 0 — chr4 152348673 152348801 461_64087_55294(FBXW7)_8 0 — chr4 152346929 152347071 461_64088_55294(FBXW7)_9 0 — chr4 152337801 152337936 461_64089_55294(FBXW7)_10 0 — chr4 152332595 152332719 461_64090_55294(FBXW7)_11 0 — chr4 152330731 152330868 461_64091_55294(FBXW7)_12 0 — chr4 152329671 152329785 461_64092_55294(FBXW7)_13 0 — chr4 152328207 152328389 461_64093_55294(FBXW7)_14 0 — chr4 152326005 152326231 461_64094_55294(FBXW7)_15 0 — chr4 152323088 152323149 461_64096_55294(FBXW7)_17 0 — chr1 26762151 26762319 426_4224_8289(ARID1A)_7a 0 — chr1 26773345 26773496 426_4232_8289(ARID1A)_15a 0 — chr10 43111206 43111465 473_148925_5979(RET)_7a 0 — chr10 43109030 43109230 473_148924_5979(RET)_6a 0 — chr10 43106375 43106571 473_148923_5979(RET)_5a 0 — chr10 43102341 43102629 473_148921_5979(RET)_3a 0 — chr10 43100458 43100722 473_148920_5979(RET)_2a 0 — chr10 43077258 43077331 473_148919_5979(RET)_1a 0 — chr13 32326100 32326150 427_15653_675(BRCA2)_5 0 — chr13 32346826 32346896 427_15661_675(BRCA2)_13 0 — chr17 43097243 43097289 427_15613_672(BRCA1)_8 0 — chr17 43070927 43071238 427_15621_672(BRCA1)_16 0 — chr17 43045677 43045802 427_15629_672(BRCA1)_24 0 — chr7 140794307 140794467 427_15637_673(BRAF)_8 0 — chr7 140749286 140749418 427_15645_673(BRAF)_16 0 — chr13 32376669 32376791 427_15669_675(BRCA2)_21 0 — chr18 51049294 51049324 474_158718_4089(SMAD4)_4 0 — chr19 2164184 2164265 431_55601_84444(DOT1L)_1 0 — chr22 29043298 29043430 478_203546_84133(ZNRF3)_7 0 — chr22 29044779 29044890 478_203547_84133(ZNRF3)_8 0 — chr22 29046715 29046883 478_203548_84133(ZNRF3)_9 0 — chr22 29049196 29050948 478_203550_84133(ZNRF3)_11 0 — chr22 29053578 29053622 478_203551_84133(ZNRF3)_12 0 — chr19 2180712 2180756 431_55602_84444(DOT1L)_2 0 — chr4 1805354 1805476 461_60345_2261(FGFR3)_12a 0 — chr4 1805558 1805669 461_60346_2261(FGFR3)_13a 0 — chr4 1805749 1805940 461_60347_2261(FGFR3)_14a 0 — chr4 1806050 1806173 461_60348_2261(FGFR3)_15a 0 — chr4 1806256 1806327 461_60349_2261(FGFR3)_16a 0 — chr4 1806545 1806683 461_60350_2261(FGFR3)_17a 0 — chr4 1807115 1807262 461_60352_2261(FGFR3)_19a 0 — chr4 1793934 1794043 461_60335_2261(FGFR3)_2a 0 — chr4 1799253 1799523 461_60336_2261(FGFR3)_3a 0 — chr4 1799746 1799812 461_60337_2261(FGFR3)_4a 0 — chr4 1801366 1801536 461_60338_2261(FGFR3)_5a 0 — chr19 2185854 2185929 431_55603_84444(DOT1L)_3 0 — chr19 2189731 2189795 431_55604_84444(DOT1L)_4 0 — chr19 2191011 2191240 431_55605_84444(DOT1L)_5 0 — chr19 2193688 2193783 431_55606_84444(DOT1L)_6 0 — chr19 2199883 2199939 431_55608_84444(DOT1L)_8 0 — chr19 2202699 2202779 431_55609_84444(DOT1L)_9 0 — chr19 2206728 2206797 431_55610_84444(DOT1L)_10 0 — chr19 2207573 2207680 431_55611_84444(DOT1L)_11 0 — chr19 2208934 2208976 431_55612_84444(DOT1L)_12 0 — chr19 2210399 2210510 431_55613_84444(DOT1L)_13 0 — chr19 2210620 2210855 431_55614_84444(DOT1L)_14 0 — chr19 2211750 2211842 431_55616_84444(DOT1L)_16 0 — chr19 2213538 2213640 431_55617_84444(DOT1L)_17 0 — chr19 2213848 2213986 431_55618_84444(DOT1L)_18 0 — chr19 2214470 2214596 431_55619_84444(DOT1L)_19 0 — chr19 2216280 2216765 431_55620_84444(DOT1L)_20 0 — chr15 66444655 66444707 465_99854_5604(MAP2K1)_6a 0 — chr15 66481754 66481879 465_99855_5604(MAP2K1)_7a 0 — chr15 66484989 66485191 465_99856_5604(MAP2K1)_8a 0 — chr15 66487227 66487292 465_99857_5604(MAP2K1)_9a 0 — chr15 66489214 66489276 465_99858_5604(MAP2K1)_10a 0 — chr15 66489717 66489763 465_99859_5604(MAP2K1)_11a 0 — chr19 2216954 2217090 431_55621_84444(DOT1L)_21 0 — chr19 2217771 2217918 431_55622_84444(DOT1L)_22 0 — chr19 2221975 2222559 431_55624_84444(DOT1L)_24 0 — chr19 2223280 2223486 431_55625_84444(DOT1L)_25 0 — chr19 2225387 2225452 431_55626_84444(DOT1L)_26 0 — chr19 2226182 2227127 431_55627_84444(DOT1L)_27 0 — chr19 2227736 2229792 431_55628_84444(DOT1L)_28 0 — chr9 5050685 5050831 463_81648_3717(JAK2)_6 0 — chr9 5055668 5055788 463_81650_3717(JAK2)_8 0 — chr9 5064882 5065040 463_81651_3717(JAK2)_9 0 — chr9 5066677 5066789 463_81652_3717(JAK2)_10 0 — chr9 5069021 5069208 463_81653_3717(JAK2)_11 0 — chr9 5069924 5070052 463_81654_3717(JAK2)_12 0 — chr9 5072491 5072626 463_81655_3717(JAK2)_13 0 — chr9 5077452 5077580 463_81657_3717(JAK2)_15 0 — chr9 5078305 5078444 463_81658_3717(JAK2)_16 0 — chr9 5080228 5080380 463_81659_3717(JAK2)_17 0 — chr9 5080532 5080683 463_81660_3717(JAK2)_18 0 — chr9 5081724 5081861 463_81661_3717(JAK2)_19 0 — chr9 5089673 5089863 463_81662_3717(JAK2)_20 0 — chr9 5090445 5090570 463_81663_3717(JAK2)_21 0 — chr9 5123003 5123121 463_81665_3717(JAK2)_23 0 — chr9 5126332 5126446 463_81666_3717(JAK2)_24 0 — chr9 5126683 5126791 463_81667_3717(JAK2)_25 0 — chr4 1801619 1801743 461_60339_2261(FGFR3)_6a 0 — chr4 1801834 1802025 461_60340_2261(FGFR3)_7a 0 — chr10 121518681 121518829 461_60359_2263(FGFR2)_9a 0 — chr10 121487353 121487424 461_60367_2263(FGFR2)_17a 0 — chr10 121593708 121593817 461_60353_2263(FGFR2)_3a 0 — chr10 121565437 121565704 461_60354_2263(FGFR2)_4a 0 — chr10 121564501 121564579 461_60355_2263(FGFR2)_5a 0 — chr10 121551289 121551459 461_60356_2263(FGFR2)_6a 0 — chr10 121538591 121538715 461_60357_2263(FGFR2)_7a 0 — chr10 121519978 121520169 461_60358_2263(FGFR2)_8a 0 — chr10 121517318 121517463 461_60360_2263(FGFR2)_10a 0 — chr10 121515116 121515319 461_60361_2263(FGFR2)_11a 0 — chr10 121503789 121503941 461_60362_2263(FGFR2)_12a 0 — chr10 121500825 121500947 461_60363_2263(FGFR2)_13a 0 — chr10 121498494 121498605 461_60364_2263(FGFR2)_14a 0 — chr10 121496531 121496722 461_60365_2263(FGFR2)_15a 0 — chr10 121487990 121488113 461_60366_2263(FGFR2)_16a 0 — chr10 121485394 121485532 461_60368_2263(FGFR2)_18a 0 — chr10 121483697 121483803 461_60369_2263(FGFR2)_19a 0 — chr10 121481850 121482177 461_60370_2263(FGFR2)_20a 0 — chr10 121479580 121480021 461_60371_2263(FGFR2)_21a 0 — chr8 38461095 38461106 461_60316_2260(FGFR1)_3a 0 — chr8 38421796 38421941 461_60324_2260(FGFR1)_11a 0 — chr8 38413917 38414023 461_60333_2260(FGFR1)_20a 0 — chr8 38457355 38457534 461_60317_2260(FGFR1)_4a 0 — chr8 38440305 38440373 461_60318_2260(FGFR1)_5a 0 — chr8 38429681 38429948 461_60319_2260(FGFR1)_6a 0 — chr8 38428345 38428435 461_60320_2260(FGFR1)_7a 0 — chr8 38427920 38428093 461_60321_2260(FGFR1)_8a 0 — chr8 38426121 38426245 461_60322_2260(FGFR1)_9a 0 — chr8 38424508 38424699 461_60323_2260(FGFR1)_10a 0 — chr8 38419532 38419735 461_60325_2260(FGFR1)_12a 0 — chr8 38418227 38418373 461_60326_2260(FGFR1)_13a 0 — chr8 38417869 38417991 461_60327_2260(FGFR1)_14a 0 — chr8 38417305 38417416 461_60328_2260(FGFR1)_15a 0 — chr8 38415869 38416060 461_60329_2260(FGFR1)_16a 0 — chr8 38414778 38414901 461_60330_2260(FGFR1)_17a 0 — chr1 64838464 64838589 463_81643_3716(JAK1)_22a 0 — chr1 64837931 64838104 463_81644_3716(JAK1)_23a 0 — chr1 64836097 64836215 463_81645_3716(JAK1)_24a 0 — chr1 64835395 64835506 463_81646_3716(JAK1)_25a 0 — chr8 38414558 38414629 461_60331_2260(FGFR1)_18a 0 — chr8 38414151 38414289 461_60332_2260(FGFR1)_19a 0 — chr8 38413627 38413804 461_60334_2260(FGFR1)_21a 0 — chr7 148832633 148832750 461_59349_2146(EZH2)_6 0 — chr7 148816683 148816778 461_59357_2146(EZH2)_14 0 — chr1 64834561 64834657 463_81647_3716(JAK1)_26a 0 — chr1 64886258 64886341 463_81624_3716(JAK1)_3a 0 — chr1 64879024 64879148 463_81626_3716(JAK1)_5a 0 — chr1 64873369 64873523 463_81627_3716(JAK1)_6a 0 — chr22 29031584 29031631 478_203544_84133(ZNRF3)_5 0 — chr7 148807645 148807706 461_59365_2146(EZH2)_22 0 — chr7 148850453 148850470 461_59346_2146(EZH2)_3 0 — chr7 148847181 148847305 461_59347_2146(EZH2)_4 0 — chr7 148846469 148846598 461_59348_2146(EZH2)_5 0 — chr7 148829727 148829848 461_59350_2146(EZH2)_7 0 — chr7 148828739 148828880 461_59351_2146(EZH2)_8 0 — chr7 148827163 148827266 461_59352_2146(EZH2)_9 0 — chr7 148826453 148826632 461_59353_2146(EZH2)_10 0 — chr7 148819595 148819687 461_59354_2146(EZH2)_11 0 — chr7 148817876 148818117 461_59355_2146(EZH2)_12 0 — chr7 148817221 148817391 461_59356_2146(EZH2)_13 0 — chr7 148815505 148815546 461_59358_2146(EZH2)_15 0 — chr7 148814913 148815039 461_59359_2146(EZH2)_16 0 — chr7 148813958 148814137 461_59360_2146(EZH2)_17 0 — chr7 148811624 148811720 461_59361_2146(EZH2)_18 0 — chr7 148810332 148810414 461_59362_2146(EZH2)_19 0 — chr7 148809309 148809390 461_59363_2146(EZH2)_20 0 — chr7 148809070 148809155 461_59364_2146(EZH2)_21 0 — chr1 64869310 64869474 463_81628_3716(JAK1)_7a 0 — chr1 64866865 64867208 463_81629_3716(JAK1)_8a 0 — chr1 64864786 64864972 463_81630_3716(JAK1)_9a 0 — chr1 64860104 64860262 463_81631_3716(JAK1)_10a 0 — chr1 64857655 64857779 463_81632_3716(JAK1)_11a 0 — chr1 64850803 64850910 463_81634_3716(JAK1)_13a 0 — chr1 64847531 64847675 463_81635_3716(JAK1)_14a 0 — chr1 64846648 64846736 463_81636_3716(JAK1)_15a 0 — chr1 64845512 64845640 463_81637_3716(JAK1)_16a 0 — chr1 64844753 64844889 463_81638_3716(JAK1)_17a 0 — chr15 90088586 90088747 463_79504_3418(IDH2)_5a 0 — chr15 90084815 90084908 463_79510_3418(IDH2)_11a 0 — chr2 208241993 208242145 463_79496_3417(IDH1)_10a 0 — chr11 534211 534322 463_79034_3265(HRAS)_2a 0 — chr13 48479997 48480071 472_141469_5925(RB1)_27a 0 — chr13 48459687 48459833 472_141462_5925(RB1)_20a 0 — chr13 48373404 48373492 472_141454_5925(RB1)_12a 0 — chr13 48347824 48347863 472_141447_5925(RB1)_5a 0 — chr17 58354942 58354986 473_154862_54894(RNF43)_10 0 — chr17 58357467 58358823 473_154861_54894(RNF43)_9 0 — chr17 58360148 58360251 473_154860_54894(RNF43)_8 0 — chr17 58360782 58360944 473_154859_54894(RNF43)_7 0 — chr17 58362543 58362648 473_154858_54894(RNF43)_6 0 — chr17 58363274 58363406 473_154857_54894(RNF43)_5 0 — chr17 58370910 58371033 473_154855_54894(RNF43)_3 0 — chr17 58415325 58415577 473_154854_54894(RNF43)_2 0 — chr22 29042494 29042569 478_203545_84133(ZNRF3)_6 0 — chr22 23834140 23834180 474_160336_6598(SMARCB1)_9 0 — chr22 23833571 23833703 474_160335_6598(SMARCB1)_8 0 — chr22 23825224 23825415 474_160334_6598(SMARCB1)_7 0 — chr22 23816769 23816936 474_160333_6598(SMARCB1)_6 0 — chr22 23803294 23803422 474_160332_6598(SMARCB1)_5 0 — chr22 23800943 23801135 474_160331_6598(SMARCB1)_4 0 — chr22 23791755 23791894 474_160329_6598(SMARCB1)_2 0 — chr22 23787169 23787262 474_160328_6598(SMARCB1)_1 0 — chr7 129212023 129212451 474_160575_6608(SMO)_12a 0 — chr7 129211635 129211770 474_160574_6608(SMO)_11a 0 — chr7 129210362 129210548 474_160572_6608(SMO)_9a 0 — chr7 129209288 129209397 474_160571_6608(SMO)_8a 0 — chr7 129208758 129208851 474_160570_6608(SMO)_7a 0 — chr7 129206463 129206587 474_160569_6608(SMO)_6a 0 — chr7 129206149 129206369 474_160568_6608(SMO)_5a 0 — chr7 129205609 129205782 474_160567_6608(SMO)_4a 0 — chr7 129203383 129203589 474_160565_6608(SMO)_2a 0 — chr7 129189151 129189482 474_160564_6608(SMO)_1a 0 — chr22 28917388 28917481 478_203541_84133(ZNRF3)_2 0 — chr22 29048388 29048491 478_203549_84133(ZNRF3)_10 0 — chr13 28070490 28070612 461_60854_2322(FLT3)_3a 0 — chr2 212124751 212124903 461_58773_2066(ERBB4)_2a 0 — chr2 211704103 211704194 461_58782_2066(ERBB4)_11a 0 — chr2 211623921 211624044 461_58790_2066(ERBB4)_19a 0 — chr2 211387944 211387992 461_58798_2066(ERBB4)_27a 0 — chr13 28037184 28037288 461_60862_2322(FLT3)_11a 0 — chr13 28024860 28024943 461_60870_2322(FLT3)_19a 0 — chr22 28883766 28884066 478_203540_84133(ZNRF3)_1 0 — chr22 28986622 28986639 478_203542_84133(ZNRF3)_3 0 — chr22 28987075 28987201 478_203543_84133(ZNRF3)_4 0 — chr4 1802913 1803064 461_60341_2261(FGFR3)_8a 0 — chr4 1804329 1804520 461_60343_2261(FGFR3)_10a 0 — chr4 1806828 1806934 461_60351_2261(FGFR3)_18a 0 — chr4 1803691 1803836 461_60342_2261(FGFR3)_9a 0 — chr4 1804823 1804969 461_60344_2261(FGFR3)_11a 0 — chr19 2194514 2194577 431_55607_84444(DOT1L)_7 0 — chr19 2211098 2211212 431_55615_84444(DOT1L)_15 0 — chr19 2220107 2220222 431_55623_84444(DOT1L)_23 0 — chr19 1221948 1222006 475_170593_6794(STK11)_7a 0 — chr19 1206913 1207203 475_170587_6794(STK11)_1a 0 — chr19 1218416 1218500 475_170588_6794(STK11)_2a 0 — chr2 211619176 211619275 461_58791_2066(ERBB4)_20a 0 — chr2 211561902 211562088 461_58792_2066(ERBB4)_21a 0 — chr2 211430944 211431100 461_58793_2066(ERBB4)_22a 0 — chr2 211428407 211428483 461_58794_2066(ERBB4)_23a 0 — chr2 211424154 211424301 461_58795_2066(ERBB4)_24a 0 — chr2 211422006 211422104 461_58796_2066(ERBB4)_25a 0 — chr2 211420440 211420611 461_58797_2066(ERBB4)_26a 0 — chr2 211386852 211387150 461_58799_2066(ERBB4)_28a 0 — chr2 211383614 211384060 461_58800_2066(ERBB4)_29a 0 — chr12 56087794 56087913 461_58655_2065(ERBB3)_6a 0 — chr12 56094098 56094189 461_58757_2065(ERBB3)_14a 0 — chr12 56098499 56098575 461_58765_2065(ERBB3)_22a 0 — chr19 1219323 1219413 475_170589_6794(STK11)_3a 0 — chr19 1220372 1220505 475_170590_6794(STK11)_4a 0 — chr19 1220580 1220717 475_170591_6794(STK11)_5a 0 — chr19 1221212 1221340 475_170592_6794(STK11)_6a 0 — chr19 1222984 1223172 475_170594_6794(STK11)_8a 0 — chr19 1223637 1226446 475_170595_6794(STK11)_9a 0 — chr19 1226453 1226663 475_170596_6794(STK11)_10a 0 — chr19 1227592 1228082 475_170597_6794(STK11)_11a 0 — chr20 37393894 37393993 475_169919_6714(SRC)_7a 0 — chr12 56099647 56099745 461_58767_2065(ERBB3)_24a 0 — chr12 56099837 56100029 461_58768_2065(ERBB3)_25a 0 — chr12 56100173 56100245 461_58769_2065(ERBB3)_26a 0 — chr12 56101060 56101361 461_58770_2065(ERBB3)_27a 0 — chr12 56101528 56102055 461_58771_2065(ERBB3)_28a 0 — chr20 37402748 37402880 475_169926_6714(SRC)_14a 0 — chr20 37384153 37384403 475_169917_6714(SRC)_5a 0 — chr20 37386074 37386174 475_169918_6714(SRC)_6a 0 — chr20 37394173 37394277 475_169920_6714(SRC)_8a 0 — chr20 37396161 37396311 475_169921_6714(SRC)_9a 0 — chr20 37397698 37397854 475_169922_6714(SRC)_10a 0 — chr20 37400114 37400294 475_169923_6714(SRC)_11a 0 — chr20 37401601 37401678 475_169924_6714(SRC)_12a 0 — chr20 37402434 37402588 475_169925_6714(SRC)_13a 0 — chr20 37403170 37403379 475_169927_6714(SRC)_15a 0 — chr15 66435026 66435237 465_99851_5604(MAP2K1)_3a 0 — chr17 39700000 39700311 461_58728_2064(ERBB2)_6a 0 — chr17 39712321 39712448 461_58736_2064(ERBB2)_14a 0 — chr17 39723318 39723457 461_58744_2064(ERBB2)_22a 0 — chr17 39726814 39727003 461_58752_2064(ERBB2)_30a 0 — chr17 39699559 39699587 461_58727_2064(ERBB2)_5a 0 — chr17 39706987 39707141 461_58729_2064(ERBB2)_7a 0 — chr17 39708320 39708534 461_58730_2064(ERBB2)_8a 0 — chr17 39709317 39709452 461_58731_2064(ERBB2)_9a 0 — chr17 39709812 39709881 461_58732_2064(ERBB2)_10a 0 — chr17 39710085 39710201 461_58733_2064(ERBB2)_11a 0 — chr17 39710339 39710481 461_58734_2064(ERBB2)_12a 0 — chr17 39711927 39712047 461_58735_2064(ERBB2)_13a 0 — chr17 39715285 39715359 461_58737_2064(ERBB2)_15a 0 — chr17 39715445 39715536 461_58738_2064(ERBB2)_16a 0 — chr17 39715739 39715939 461_58739_2064(ERBB2)_17a 0 — chr17 39716300 39716433 461_58740_2064(ERBB2)_18a 0 — chr17 39716514 39716605 461_58741_2064(ERBB2)_19a 0 — chr17 39717319 39717480 461_58742_2064(ERBB2)_20a 0 — chr17 39719786 39719834 461_58743_2064(ERBB2)_21a 0 — chr17 39723537 39723660 461_58745_2064(ERBB2)_23a 0 — chr17 39723911 39724010 461_58746_2064(ERBB2)_24a 0 — chr17 39724725 39724911 461_58747_2064(ERBB2)_25a 0 — chr17 39725048 39725204 461_58748_2064(ERBB2)_26a 0 — chr17 39725326 39725402 461_58749_2064(ERBB2)_27a 0 — chr17 39725706 39725853 461_58750_2064(ERBB2)_28a 0 — chr17 39726561 39726659 461_58751_2064(ERBB2)_29a 0 — chr17 39727294 39727547 461_58753_2064(ERBB2)_31a 0 — chr17 39727688 39728044 461_58754_2064(ERBB2)_32a 0 — chr15 66490501 66490615 465_99860_5604(MAP2K1)_12a 0 — chr15 66387347 66387427 465_99849_5604(MAP2K1)_1a 0 — chr15 66401862 66401947 465_99850_5604(MAP2K1)_2a 0 — chr15 66436745 66436892 465_99852_5604(MAP2K1)_4a 0 — chr15 66443279 66443357 465_99853_5604(MAP2K1)_5a 0 — chr1 113585386 113585596 465_103739_260425(MAGI3)_4 0 — chr1 113643742 113643774 465_103747_260425(MAGI3)_12 0 — chr1 113673321 113673465 465_103755_260425(MAGI3)_20 0 — chr1 113391033 113391349 465_103736_260425(MAGI3)_1 0 — chr1 113549514 113549631 465_103737_260425(MAGI3)_2 0 — chr1 113580541 113580661 465_103738_260425(MAGI3)_3 0 — chr1 113590483 113590658 465_103740_260425(MAGI3)_5 0 — chr17 31356459 31356582 469_118625_4763(NF1)_52a 0 — chr17 31352256 31352414 469_118624_4763(NF1)_51a 0 — chr17 31350182 31350318 469_118623_4763(NF1)_50a 0 — chr1 26774328 26775220 426_4235_8289(ARID1A)_18a 0 — chr1 26775576 26775707 426_4236_8289(ARID1A)_19a 0 — chr1 26779022 26780756 426_4237_8289(ARID1A)_20a 0 — chr5 112801278 112801383 426_2913_324(APC)_11a 0 — chr5 112837552 112844126 426_2921_324(APC)_19a 0 — chr5 112707717 112707882 426_2903_324(APC)_1a 0 — chr5 112737858 112737925 426_2904_324(APC)_2a 0 — chr5 112738331 112738460 426_2905_324(APC)_3a 0 — chr5 112754872 112755025 426_2906_324(APC)_4a 0 — chr5 112755074 112755094 426_2907_324(APC)_5a 0 — chr5 112766325 112766410 426_2908_324(APC)_6a 0 — chr5 112767188 112767390 426_2909_324(APC)_7a 0 — chr5 112775628 112775737 426_2910_324(APC)_8a 0 — chr5 112780789 112780903 426_2911_324(APC)_9a 0 — chr5 112792445 112792529 426_2912_324(APC)_10a 0 — chr5 112815494 112815593 426_2914_324(APC)_12a 0 — chr5 112818965 112819344 426_2915_324(APC)_13a 0 — chr5 112821895 112821991 426_2916_324(APC)_14a 0 — chr5 112827107 112827247 426_2917_324(APC)_15a 0 — chr5 112827928 112828006 426_2918_324(APC)_16a 0 — chr1 113594480 113594560 465_103741_260425(MAGI3)_6 0 — chr16 68801669 68801893 428_25422_999(CDH1)_3 0 — chr16 68815514 68815759 428_25429_999(CDH1)_10 0 — chr16 68737415 68737463 428_25420_999(CDH1)_1 0 — chr16 68738296 68738411 428_25421_999(CDH1)_2 0 — chr16 68808423 68808567 428_25423_999(CDH1)_4 0 — chr1 113614600 113614658 465_103742_260425(MAGI3)_70 0 — chr1 113618531 113618606 465_103743_260425(MAGI3)_80 0 — chr1 113619735 113619830 465_103744_260425(MAGI3)_90 0 — chr1 113622805 113622994 465_103745_260425(MAGI3)_10 0 — chr1 113641910 113642516 465_103746_260425(MAGI3)_11 0 — chr1 113646485 113646642 465_103748_260425(MAGI3)_13 0 — chr1 113649236 113649328 465_103749_260425(MAGI3)_14 0 — chr1 113651013 113651206 465_103750_260425(MAGI3)_15 0 — chr1 113653829 113654018 465_103751_260425(MAGI3)_16 0 — chr1 113659079 113659265 465_103752_260425(MAGI3)_17 0 — chr1 113671733 113671836 465_103753_260425(MAGI3)_18 0 — chr1 113672614 113672741 465_103754_260425(MAGI3)_19 0 — chr1 113681197 113681336 465_103756_260425(MAGI3)_21 0 — chr1 113682211 113684014 465_103757_260425(MAGI3)_22 0 — chr16 68808692 68808848 428_25424_999(CDH1)_5 0 — chr16 68810196 68810341 428_25425_999(CDH1)_6 0 — chr16 68811683 68811859 428_25426_999(CDH1)_7 0 — chr16 68812134 68812263 428_25427_999(CDH1)_8 0 — chr16 68813312 68813495 428_25428_999(CDH1)_9 0 — chr7 152315137 152315338 464_94967_58508(KMT2C)_4 0 — chr7 152249875 152249953 464_94976_58508(KMT2C)_13 0 — chr7 152222572 152222682 464_94984_58508(KMT2C)_21 0 — chr7 152194439 152194568 464_94993_58508(KMT2C)_30 0 — chr7 152171263 152171342 464_95004_58508(KMT2C)_41 0 — chr7 152154009 152154146 464_95013_58508(KMT2C)_50 0 — chr7 152139674 152139791 464_95021_58508(KMT2C)_58 0 — chr16 68819279 68819425 428_25430_999(CDH1)_11 0 — chr7 152180710 152182594 464_95000_58508(KMT2C)_37 0 — chr7 152179833 152180126 464_95001_58508(KMT2C)_38 0 — chr7 152176190 152178010 464_95002_58508(KMT2C)_39 0 — chr7 152174130 152174242 464_95003_58508(KMT2C)_40 0 — chr7 152169185 152169249 464_95005_58508(KMT2C)_42 0 — chr7 152167145 152167378 464_95006_58508(KMT2C)_43 0 — chr7 152162116 152163826 464_95007_58508(KMT2C)_44 0 — chr7 152158856 152159072 464_95008_58508(KMT2C)_45 0 — chr7 152157760 152157925 464_95009_58508(KMT2C)_46 0 — chr7 152156204 152156346 464_95010_58508(KMT2C)_47 0 — chr7 152155909 152156057 464_95011_58508(KMT2C)_48 0 — chr7 152154266 152154445 464_95012_58508(KMT2C)_49 0 — chr7 152152704 152152954 464_95014_58508(KMT2C)_51 0 — chr7 152151441 152151581 464_95015_58508(KMT2C)_52 0 — chr7 152150899 152151007 464_95016_58508(KMT2C)_53 0 — chr7 152148032 152149152 464_95017_58508(KMT2C)_54 0 — chr7 152146598 152146735 464_95018_58508(KMT2C)_55 0 — chr7 152145152 152145295 464_95019_58508(KMT2C)_56 0 — chr7 152144712 152144881 464_95020_58508(KMT2C)_57 0 — chr7 152435625 152435786 464_94964_58508(KMT2C)_1 0 — chr7 152358586 152358675 464_94965_58508(KMT2C)_2 0 — chr7 152330600 152330742 464_94966_58508(KMT2C)_3 0 — chr7 152311797 152311946 464_94968_58508(KMT2C)_5 0 — chr7 152309965 152310075 464_94969_58508(KMT2C)_6 0 — chr7 152273704 152273867 464_94970_58508(KMT2C)_7 0 — chr7 152265037 152265209 464_94971_58508(KMT2C)_8 0 — chr7 152263015 152263130 464_94972_58508(KMT2C)_9 0 — chr7 152252545 152252715 464_94973_58508(KMT2C)_1 0 — chr16 68822000 68822225 428_25431_999(CDH1)_12 0 — chr7 152251938 152252090 464_94974_58508(KMT2C)_11 0 — chr7 152250852 152250966 464_94975_58508(KMT2C)_12 0 — chr7 152247901 152248620 464_94977_58508(KMT2C)_14 0 — chr7 152238706 152238826 464_94978_58508(KMT2C)_15 0 — chr7 152235816 152235933 464_94979_58508(KMT2C)_16 0 — chr7 152230219 152230321 464_94980_58508(KMT2C)_17 0 — chr7 152229922 152230027 464_94981_58508(KMT2C)_18 0 — chr5 112828855 112828972 426_2919_324(APC)_17a 0 — chr5 112834950 112835165 426_2920_324(APC)_18a 0 — chr14 104777568 104777740 426_1772_207(AKT1)_6a 0 — chr14 104776658 104776770 426_1773_207(AKT1)_7a 0 — chr14 104775075 104775207 426_1775_207(AKT1)_9a 0 — chr14 104774937 104775003 426_1776_207(AKT1)_10a 0 — chr14 104773911 104773980 426_1777_207(AKT1)_11a 0 — chr14 104773454 104773580 426_1778_207(AKT1)_12a 0 — chr14 104773250 104773379 426_1779_207(AKT1)_13a 0 — chr14 104772877 104773092 426_1780_207(AKT1)_14a 0 — chr14 104772364 104772452 426_1781_207(AKT1)_15a 0 — chr14 104770340 104770420 426_1783_207(AKT1)_17a 0 — chr9 130714319 130714455 426_351_25(ABL1)_1 0 — chr9 130835443 130835525 426_352_25(ABL1)_2 0 — chr7 152224434 152224616 464_94982_58508(KMT2C)_19 0 — chr1 11258484 11258593 466_105882_2475(MTOR)_3a 0 — chr1 11243113 11243300 466_105889_2475(MTOR)_10a 0 — chr1 11231299 11231434 466_105897_2475(MTOR)_18a 0 — chr1 11209311 11209458 466_105905_2475(MTOR)_26a 0 — chr1 11146675 11146791 466_105912_2475(MTOR)_33a 0 — chr1 11129737 11129838 466_105920_2475(MTOR)_41a 0 — chr1 11121978 11122126 466_105928_2475(MTOR)_49a 0 — chr1 11109648 11109729 466_105935_2475(MTOR)_56a 0 — chr7 152139185 152139259 464_95022_58508(KMT2C)_59 0 — chr7 140801411 140801560 427_15635_673(BRAF)_6 0 — chr7 140800361 140800481 427_15636_673(BRAF)_7 0 — chr16 68823398 68823626 428_25432_999(CDH1)_13 0 — chr16 68828173 68828304 428_25433_999(CDH1)_14 0 — chr16 68829653 68829797 428_25434_999(CDH1)_15 0 — chr16 68833289 68833499 428_25435_999(CDH1)_16 0 — chr7 152138795 152138904 464_95023_58508(KMT2C)_60 0 — chr7 152136831 152136924 464_95024_58508(KMT2C)_61 0 — chr9 130883968 130885683 426_362_25(ABL1)_12 0 — chr9 130862762 130863035 426_355_25(ABL1)_5 0 — chr13 32316460 32316527 427_15650_675(BRCA2)_2 0 — chr13 32319076 32319325 427_15651_675(BRCA2)_3 0 — chr13 32325075 32325184 427_15652_675(BRCA2)_4 0 — chr13 32326241 32326282 427_15654_675(BRCA2)_6 0 — chr13 32326498 32326613 427_15655_675(BRCA2)_7 0 — chr13 32329442 32329492 427_15656_675(BRCA2)_8 0 — chr13 32330918 32331030 427_15657_675(BRCA2)_9 0 — chr13 32332271 32333387 427_15658_675(BRCA2)_10 0 — chr13 32336264 32341196 427_15659_675(BRCA2)_11 0 — chr13 32344557 32344653 427_15660_675(BRCA2)_12 0 — chr13 32354897 32355325 427_15662_675(BRCA2)_14 0 — chr13 32356427 32356609 427_15663_675(BRCA2)_15 0 — chr4 54698283 54698565 464_88968_3815(KIT)_3 0 — chr4 54727217 54727324 464_88975_3815(KIT)_10 0 — chr4 54736497 54736609 464_88983_3815(KIT)_18 0 — chr4 54658014 54658081 464_88966_3815(KIT)_1 0 — chr4 54695511 54695781 464_88967_3815(KIT)_2 0 — chr4 54699629 54699766 464_88969_3815(KIT)_4 0 — chr6 152098731 152098966 461_58886_2099(ESR1)_12 0 — chr6 151807912 151808364 461_58879_2099(ESR1)_5 0 — chr6 151842596 151842793 461_58880_2099(ESR1)_6 0 — chr6 151880654 151880771 461_58881_2099(ESR1)_7 0 — chr6 151944172 151944508 461_58882_2099(ESR1)_8 0 — chr6 152011655 152011794 461_58883_2099(ESR1)_9 0 — chr4 54703720 54703892 464_88970_3815(KIT)_5 0 — chr4 54707097 54707287 464_88971_3815(KIT)_6 0 — chr4 54709423 54709539 464_88972_3815(KIT)_7 0 — chr4 54723583 54723698 464_88973_3815(KIT)_8 0 — chr4 54725856 54726050 464_88974_3815(KIT)_9 0 — chr4 54727415 54727542 464_88976_3815(KIT)_11 0 — chr4 54727822 54727927 464_88977_3815(KIT)_12 0 — chr4 54728010 54728121 464_88978_3815(KIT)_13 0 — chr4 54729334 54729485 464_88979_3815(KIT)_14 0 — chr4 54731327 54731419 464_88980_3815(KIT)_15 0 — chr4 54731870 54731998 464_88981_3815(KIT)_16 0 — chr4 54733069 54733192 464_88982_3815(KIT)_17 0 — chr7 140787547 140787584 427_15638_673(BRAF)_9 0 — chr7 140783020 140783157 427_15639_673(BRAF)_10 0 — chr7 140781575 140781693 427_15640_673(BRAF)_11 0 — chr7 140777990 140778075 427_15641_673(BRAF)_12 0 — chr7 140776911 140777088 427_15642_673(BRAF)_13 0 — chr7 140754186 140754233 427_15643_673(BRAF)_14 0 — chr7 140753274 140753393 427_15644_673(BRAF)_15 0 — chr7 140747365 140747447 427_15646_673(BRAF)_17 0 — chr7 140739811 140739946 427_15647_673(BRAF)_18 0 — chr7 140734011 140734770 427_15648_673(BRAF)_19 0 — chr4 54736720 54736820 464_88984_3815(KIT)_19 0 — chr7 140719333 140726516 427_15649_673(BRAF)_20 0 — chr9 130854063 130854237 426_353_25(ABL1)_3 0 — chr9 130854800 130855096 426_354_25(ABL1)_4 0 — chr1 26696403 26697540 426_4218_8289(ARID1A)_1a 0 — chr1 26729650 26729863 426_4219_8289(ARID1A)_2a 0 — chr1 26731151 26731604 426_4220_8289(ARID1A)_3a 0 — chr1 26732675 26732792 426_4221_8289(ARID1A)_4a 0 — chr4 54737174 54737280 464_88985_3815(KIT)_20 0 — chr1 26760855 26761096 426_4222_8289(ARID1A)_5a 0 — chr1 26761383 26761473 426_4223_8289(ARID1A)_6a 0 — chr5 56884663 56884826 465_99634_4214(MAP3K1)_18a 0 — chr5 56887377 56887520 465_99636_4214(MAP3K1)_20a 0 — chr5 56888225 56888357 465_99637_4214(MAP3K1)_21a 0 — chr5 56893530 56893680 465_99638_4214(MAP3K1 )_22a 0 — chr17 12110374 12110426 465_99954_6416(MAP2K4)_8 0 — chr1 26762972 26763285 426_4225_8289(ARID1A)_8a 0 — chr1 26766220 26766366 426_4226_8289(ARID1A)_9a 0 — chr13 32357741 32357929 427_15664_675(BRCA2)_16 0 — chr2 29296887 29297057 426_1978_238(ALK)_9 0 — chr2 29275401 29275496 426_1979_238(ALK)_10 0 — chr2 29275098 29275227 426_1980_238(ALK)_11 0 — chr2 29251104 29251267 426_1981_238(ALK)_12 0 — chr2 29239679 29239830 426_1982_238(ALK)_13 0 — chr2 29232303 29232448 426_1984_238(ALK)_15 0 — chr2 29228883 29229066 426_1985_238(ALK)_16 0 — chr2 29227573 29227672 426_1986_238(ALK)_17 0 — chr2 29226921 29227074 426_1987_238(ALK)_18 0 — chr2 29225460 29225565 426_1988_238(ALK)_19 0 — chr2 29223341 29223528 426_1989_238(ALK)_20 0 — chr2 29222516 29222607 426_1990_238(ALK)_21 0 — chr2 29222343 29222408 426_1991_238(ALK)_22 0 — chr2 29213983 29214081 426_1993_238(ALK)_24 0 — chr2 29209785 29209878 426_1994_238(ALK)_25 0 — chr2 29207170 29207272 426_1995_238(ALK)_26 0 — chr2 29197541 29197676 426_1996_238(ALK)_27 0 — chr3 142559250 142559441 427_14859_545(ATR)_7 0 — chr3 142550131 142550302 427_14866_545(ATR)_14 0 — chr3 142538481 142538625 427_14871_545(ATR)_19 0 — chr3 142513500 142513638 427_14878_545(ATR)_26 0 — chr3 142496360 142496520 427_14886_545(ATR)_34 0 — chr3 142461939 142462090 427_14894_545(ATR)_42 0 — chr2 29196769 29196860 426_1997_238(ALK)_28 0 — chr2 29193223 29193922 426_1998_238(ALK)_29 0 — chr14 104775651 104775799 426_1774_207(AKT1)_8a 0 — chr14 104770744 104770847 426_1782_207(AKT1)_16a 0 — chr14 104792597 104792643 426_1770_207(AKT1)_4a 0 — chr14 104780087 104780216 426_1771_207(AKT1)_5a 0 — chr4 54738428 54738557 464_88986_3815(KIT)_21 0 — chr2 29328349 29328481 426_1975_238(ALK)_6 0 — chr2 29233564 29233696 426_1983_238(ALK)_14 0 — chr2 29220705 29220835 426_1992_238(ALK)_23 0 — chr2 29919992 29920659 426_1970_238(ALK)_1 0 — chr2 29717577 29717697 426_1971_238(ALK)_2 0 — chr2 29694849 29695014 426_1972_238(ALK)_3 0 — chr2 29531914 29532116 426_1973_238(ALK)_4 0 — chr2 29383731 29383859 426_1974_238(ALK)_5 0 — chr2 29320750 29320882 426_1976_238(ALK)_7 0 — chr1 26766456 26766566 426_4227_8289(ARID1A)_10a 0 — chr1 26767789 26767999 426_4228_8289(ARID1A)_11a 0 — chr9 130872128 130872213 426_356_25(ABL1)_6 0 — chr9 130872859 130873037 426_357_25(ABL1)_7 0 — chr9 130874867 130875052 426_358_25(ABL1)_8 0 — chr9 130878414 130878567 426_359_25(ABL1)_9 0 — chr9 130880067 130880157 426_360_25(ABL1)_10 0 — chr9 130880499 130880664 426_361_25(ABL1)_11 0 — chr13 32362522 32362693 427_15665_675(BRCA2)_17 0 — chr13 32363178 32363533 427_15666_675(BRCA2)_18 0 — chr13 32370401 32370557 427_15667_675(BRCA2)_19 0 — chr13 32370955 32371100 427_15668_675(BRCA2)_20 0 — chr18 51078255 51078467 474_158727_4089(SMAD4)_13 0 — chr18 51077306 51077419 474_158726_4089(SMAD4)_12 0 — chr18 51067018 51067187 474_158724_4089(SMAD4)_10 0 — chr18 51065422 51065606 474_158723_4089(SMAD4)_9 0 — chr18 51059865 51059916 474_158722_4089(SMAD4)_8 0 — chr18 51058339 51058456 474_158721_4089(SMAD4)_7 0 — chr18 51058124 51058244 474_158720_4089(SMAD4)_6 0 — chr18 51054780 51054993 474_158719_4089(SMAD4)_5 0 — chr18 51048685 51048860 474_158717_4089(SMAD4)_3 0 — chr18 51047046 51047295 474_158716_4089(SMAD4)_2 0 — chr18 51076637 51076776 474_158725_4089(SMAD4)_11 0 — chr9 77922160 77922345 462_70176_2776(GNAQ)_2 0 — chr13 32379316 32379515 427_15670_675(BRCA2)_22 0 — chr11 108235669 108235834 427_14214_472(ATM)_8 0 — chr6 152060990 152061124 461_58884_2099(ESR1)_10 0 — chr6 152094384 152094568 461_58885_2099(ESR1)_11 0 — chr13 32379749 32379913 427_15671_675(BRCA2)_23 0 — chr13 32380006 32380145 427_15672_675(BRCA2)_24 0 — chr13 32394688 32394933 427_15673_675(BRCA2)_25 0 — chr13 32396897 32397044 427_15674_675(BRCA2)_26 0 — chr13 32398161 32398770 427_15675_675(BRCA2)_27 0 — chr2 29318303 29318404 426_1977_238(ALK)_8 0 — chr1 26771118 26771326 426_4229_8289(ARID1A)_12a 0 — chr1 26772499 26772632 426_4230_8289(ARID1A)_13a 0 — chr1 26772811 26772987 426_4231_8289(ARID1A)_14a 0 — chr1 26773579 26773717 426_4233_8289(ARID1A)_16a 0 — chr1 26773801 26773898 426_4234_8289(ARID1A)_17a 0 — chr13 28100467 28100510 461_60853_2322(FLT3)_2a 0 — chr13 28061866 28062069 461_60855_2322(FLT3)_4a 0 — chr13 28057346 28057462 461_60856_2322(FLT3)_5a 0 — chr13 28052544 28052674 461_60857_2322(FLT3)_6a 0 — chr13 28050094 28050222 461_60858_2322(FLT3)_7a 0 — chr13 28049634 28049774 461_60859_2322(FLT3)_8a 0 — chr13 28049383 28049537 461_60860_2322(FLT3)_9a 0 — chr13 28048274 28048443 461_60861_2322(FLT3)_10a 0 — chr13 28035934 28036043 461_60863_2322(FLT3)_12a 0 — chr13 28035494 28035673 461_60864_2322(FLT3)_13a 0 — chr13 28034300 28034407 461_60865_2322(FLT3)_14a 0 — chr13 28034081 28034214 461_60866_2322(FLT3)_15a 0 — chr13 28033886 28033991 461_60867_2322(FLT3)_16a 0 — chr13 28028177 28028288 461_60868_2322(FLT3)_17a 0 — chr13 28027087 28027241 461_60869_2322(FLT3)_18a 0 — chr13 28023349 28023477 461_60871_2322(FLT3)_20a 0 — chr13 28018466 28018589 461_60872_2322(FLT3)_21a 0 — chr13 28015589 28015701 461_60873_2322(FLT3)_22a 0 — chr13 28015156 28015256 461_60874_2322(FLT3)_23a 0 — chr13 28014451 28014557 461_60875_2322(FLT3)_24a 0 — chr17 43124016 43124096 427_15607_672(BRCA1)_2 0 — chr17 43115725 43115779 427_15608_672(BRCA1)_3 0 — chr17 43106455 43106533 427_15609_672(BRCA1)_4 0 — chr17 43104867 43104956 427_15610_672(BRCA1)_5 0 — chr17 43104121 43104261 427_15611_672(BRCA1)_6 0 — chr17 43099774 43099880 427_15612_672(BRCA1)_7 0 — chr17 43095845 43095922 427_15614_672(BRCA1)_9 0 — chr17 43091434 43094860 427_15615_672(BRCA1)_10 0 — chr17 43090943 43091032 427_15616_672(BRCA1)_11 0 — chr17 43082403 43082575 427_15617_672(BRCA1)_12 0 — chr17 43079333 43079399 427_15618_672(BRCA1)_13 0 — chr17 43076487 43076614 427_15619_672(BRCA1)_14 0 — chr17 43074330 43074521 427_15620_672(BRCA1)_15 0 — chr17 43067607 43067695 427_15622_672(BRCA1)_17 0 — chr17 43063873 43063951 427_15623_672(BRCA1)_18 0 — chr17 43063332 43063373 427_15624_672(BRCA1)_19 0 — chr17 43057051 43057135 427_15625_672(BRCA1)_20 0 — chr17 43051062 43051117 427_15626_672(BRCA1)_21 0 — chr17 43049120 43049194 427_15627_672(BRCA1)_22 0 — chr17 43047642 43047703 427_15628_672(BRCA1)_23 0 — chr7 140924565 140924756 427_15630_673(BRAF)_1 0 — chr7 140850110 140850212 427_15631_673(BRAF)_2 0 — chr7 140834608 140834872 427_15632_673(BRAF)_3 0 — chr7 140808891 140808995 427_15633_673(BRAF)_4 0 — chr7 140807959 140808062 427_15634_673(BRAF)_5 0 — chr13 28004051 28004174 461_60876_2322(FLT3)_25a 0 — chr2 211657753 211657828 461_58788_2066(ERBB4)_17a 0 — chr11 108365081 108365218 427_14272_472(ATM)_66 0 — chr11 108365324 108365508 427_14273_472(ATM)_67 0 — chr2 211630461 211630594 461_58789_2066(ERBB4)_18a 0 — chr12 56080300 56080382 461_58650_2065(ERBB3)_1a 0 — chr12 56083750 56083902 461_58651_2065(ERBB3)_2a 0 — chr12 56084994 56085617 461_58652_2065(ERBB3)_3a 0 — chr12 56086530 56086656 461_58653_2065(ERBB3)_4a 0 — chr12 56087576 56087642 461_58654_2065(ERBB3)_5a 0 — chr12 56088020 56088162 461_58656_2065(ERBB3)_7a 0 — chr12 56088542 56088656 461_58657_2065(ERBB3)_8a 0 — chr12 56088747 56088868 461_58658_2065(ERBB3)_9a 0 — chr12 56092746 56092820 461_58659_2065(ERBB3)_10a 0 — chr12 56092985 56093076 461_58660_2065(ERBB3)_11a 0 — chr12 56093344 56093550 461_58755_2065(ERBB3)_12a 0 — chr7 55019277 55019365 431_48541_1956(EGFR)_1 0 — chr7 55109722 55109958 431_48542_1956(EGFR)_2 0 — chr7 55142285 55142437 431_48543_1956(EGFR)_3 0 — chr7 55146605 55146740 431_48545_1956(EGFR)_5 0 — chr7 55151293 55151362 431_48546_1956(EGFR)_6 0 — chr7 55152545 55152664 431_48547_1956(EGFR)_7 0 — chr7 55154010 55154152 431_48548_1956(EGFR)_8 0 — chr7 55155829 55155946 431_48549_1956(EGFR)_9 0 — chr7 55156532 55156659 431_48550_1956(EGFR)_10 0 — chr7 55156758 55156951 431_48551_1956(EGFR)_11 0 — chr7 55160138 55160338 431_48553_1956(EGFR)_13 0 — chr7 55161498 55161631 431_48554_1956(EGFR)_14 0 — chr7 55163732 55163823 431_48555_1956(EGFR)_15 0 — chr1 162741585 162741712 431_48985_4921(DDR2)_7a 0 — chr1 162767228 162767359 431_48993_4921(DDR2)_15a 0 — chr1 162780111 162780246 431_49000_4921(DDR2)_22a 0 — chr1 162711291 162711300 431_48982_4921(DDR2)_4a 0 — chr1 162719036 162719145 431_48983_4921(DDR2)_5a 0 — chr1 162719190 162719214 431_48984_4921(DDR2)_6a 0 — chr1 162753094 162753197 431_48986_4921(DDR2)_8a 0 — chr1 162754623 162754855 431_48987_4921(DDR2)_9a 0 — chr1 162755155 162755303 431_48988_4921(DDR2)_10a 0 — chr1 162755663 162755769 431_48989_4921(DDR2)_11a 0 — chr1 162759795 162759979 431_48990_4921(DDR2)_12a 0 — chr1 162761210 162761454 431_48991_4921(DDR2)_13a 0 — chr1 162766000 162766063 431_48992_4921(DDR2)_14a 0 — chr1 162770301 162770512 431_48994_4921(DDR2)_16a 0 — chr1 162772023 162772247 431_48995_4921(DDR2)_17a 0 — chr1 162773468 162773596 431_48996_4921(DDR2)_18a 0 — chr1 162775651 162775843 431_48997_4921(DDR2)_19a 0 — chr1 162776135 162776370 431_48998_4921(DDR2)_20a 0 — chr1 162778579 162778729 431_48999_4921(DDR2)_21a 0 — chr3 41225333 41225572 429_36859_1499(CTNNB1)_10 0 — chr3 41236587 41236709 429_36867_1499(CTNNB1)_18 0 — chr3 41224068 41224081 429_36856_1499(CTNNB1)_7 0 — chr3 41224525 41224753 429_36857_1499(CTNNB1)_8 0 — chr3 41224953 41225207 429_36858_1499(CTNNB1)_9 0 — chr12 25245273 25245395 464_89186_3845(KRAS)_2 0 — chr12 25227233 25227412 464_89187_3845(KRAS)_3 0 — chr12 25225613 25225773 464_89188_3845(KRAS)_4 0 — chr3 41225659 41225861 429_36860_1499(CTNNB1)_11 0 — chr3 41227207 41227352 429_36861_1499(CTNNB1)_12 0 — chr3 41233340 41233444 429_36862_1499(CTNNB1)_13 0 — chr3 41233528 41233867 429_36863_1499(CTNNB1)_14 0 — chr3 41234138 41234297 429_36864_1499(CTNNB1)_15 0 — chr12 25215149 25215560 464_89189_3845(KRAS)_5 0 — chr12 25209510 25209911 464_89190_3845(KRAS)_6 0 — chr3 41235723 41235843 429_36865_1499(CTNNB1)_16 0 — chr3 41236348 41236499 429_36866_1499(CTNNB1)_17 0 — chr3 41238015 41238076 429_36868_1499(CTNNB1)_19 0 — chr3 41239133 41239342 429_36869_1499(CTNNB1)_20 0 — chr5 150073300 150073493 429_36458_1436(CSF1R)_7a 0 — chr5 150059699 150059862 429_36466_1436(CSF1R)_15a 0 — chr9 21971328 21971400 428_25765_1029(CDKN2A)_4a 0 — chr9 21994138 21994454 428_25762_1029(CDKN2A)_1a 0 — chr9 21991594 21992480 428_25763_1029(CDKN2A)_2a 0 — chr9 21974403 21975133 428_25764_1029(CDKN2A)_3a 0 — chr9 21970901 21971208 428_25766_1029(CDKN2A)_5a 0 — chr9 21968469 21968771 428_25767_1029(CDKN2A)_6a 0 — chr9 21968228 21968242 428_25768_1029(CDKN2A)_7a 0 — chr12 12717839 12718314 428_25760_1027(CDKN1B)_1a 0 — chr12 12718824 12718946 428_25761_1027(CDKN1B)_2a 0 — chr12 112419111 112419125 472_140049_5781(PTPN11)_1a 0 — chr12 112450317 112450512 472_140051_5781(PTPN11)_3a 0 — chr12 112453194 112453387 472_140052_5781(PTPN11)_4a 0 — chr12 112454563 112454680 472_140053_5781(PTPN11)_5a 0 — chr12 112455949 112456063 472_140054_5781(PTPN11)_6a 0 — chr12 112472943 112473040 472_140055_5781(PTPN11)_7a 0 — chr12 112477650 112477730 472_140056_5781(PTPN11)_8a 0 — chr12 112477856 112478015 472_140057_5781(PTPN11)_9a 0 — chr12 112486474 112486923 472_140059_5781(PTPN11)_11a 0 — chr12 112488442 112488510 472_140060_5781(PTPN11)_12a 0 — chr12 112489023 112489175 472_140061_5781(PTPN11)_13a 0 — chr12 112502143 112502256 472_140062_5781(PTPN11)_14a 0 — chr12 112504694 112504764 472_140063_5781(PTPN11)_15a 0 — chr10 87864468 87864547 472_139786_5728(PTEN)_1 0 — chr10 87894024 87894109 472_139787_5728(PTEN)_2 0 — chr10 87925512 87925557 472_139788_5728(PTEN)_3 0 — chr10 87931045 87931089 472_139789_5728(PTEN)_4 0 — chr10 87933012 87933251 472_139790_5728(PTEN)_5 0 — chr10 87957852 87958019 472_139792_5728(PTEN)_7 0 — chr10 87960893 87961118 472_139793_5728(PTEN)_8 0 — chr10 87965286 87965472 472_139794_5728(PTEN)_9 0 — chr1 11259247 11259415 466_105881_2475(MTOR)_20 0 — chr1 11256932 11257165 466_105883_2475(MTOR)_4a 0 — chr1 11256284 11256302 466_105884_2475(MTOR)_5a 0 — chr1 11255991 11256192 466_105885_2475(MTOR)_6a 0 — chr1 11253838 11253973 466_105886_2475(MTOR)_7a 0 — chr1 11247818 11248094 466_105887_2475(MTOR)_8a 0 — chr1 11247624 11247733 466_105888_2475(MTOR)_9a 0 — chr1 11241552 11241681 466_105890_2475(MTOR)_11a 0 — chr1 11240302 11240547 466_105891_2475(MTOR)_12a 0 — chr1 11238401 11238617 466_105892_2475(MTOR)_13a 0 — chr7 152224014 152224179 464_94983_58508(KMT2C)_20 0 — chr7 152222000 152222066 464_94985_58508(KMT2C)_22 0 — chr1 11237842 11238048 466_105893_2475(MTOR)_14a 0 — chr1 11234142 11234265 466_105894_2475(MTOR)_15a 0 — chr7 152220522 152220735 464_94986_58508(KMT2C)_23 0 — chr1 11233397 11233487 466_105895_2475(MTOR)_16a 0 — chr1 11232435 11232528 466_105896_2475(MTOR)_17a 0 — chr1 11230924 11231054 466_105898_2475(MTOR)_19a 0 — chr1 11228667 11228918 466_105899_2475(MTOR)_20a 0 — chr1 11216147 11216234 466_105900_2475(MTOR)_21a 0 — chr1 11213398 11213566 466_105901_2475(MTOR)_22a 0 — chr1 11212795 11212908 466_105902_2475(MTOR)_23a 0 — chr1 11212311 11212474 466_105903_2475(MTOR)_24a 0 — chr7 152207299 152207428 464_94987_58508(KMT2C)_24 0 — chr1 11210813 11210906 466_105904_2475(MTOR)_25a 0 — chr1 11204560 11204703 466_105906_2475(MTOR)_27a 0 — chr1 11199540 11199703 466_105907_2475(MTOR)_28a 0 — chr1 11199257 11199403 466_105908_2475(MTOR)_29a 0 — chr7 152205105 152205225 464_94988_58508(KMT2C)_25 0 — chr7 152202933 152203064 464_94989_58508(KMT2C)_26 0 — chr7 152199278 152199459 464_94990_58508(KMT2C)_27 0 — chr7 152195906 152196011 464_94991_58508(KMT2C)_28 0 — chr7 152195521 152195569 464_94992_58508(KMT2C)_29 0 — chr7 152194228 152194261 464_94994_58508(KMT2C)_31 0 — chr7 152194008 152194128 464_94995_58508(KMT2C)_32 0 — chr7 152187714 152187847 464_94996_58508(KMT2C)_33 0 — chr7 152187261 152187476 464_94997_58508(KMT2C)_34 0 — chr7 152185557 152185631 464_94998_58508(KMT2C)_35 0 — chr7 152182973 152183156 464_94999_58508(KMT2C)_36 0 — chr1 11167441 11167517 466_105909_2475(MTOR)_30a 0 — chr1 11157151 11157291 466_105910_2475(MTOR)_31a 0 — chr1 11150125 11150226 466_105911_2475(MTOR)_32a 0 — chr1 11144967 11145045 466_105913_2475(MTOR)_34a 0 — chr1 11144647 11144755 466_105914_2475(MTOR)_35a 0 — chr1 11139528 11139658 466_105915_2475(MTOR)_36a 0 — chr1 11139303 11139435 466_105916_2475(MTOR)_37a 0 — chr1 11134350 11134466 466_105917_2475(MTOR)_38a 0 — chr1 11133079 11133197 466_105918_2475(MTOR)_39a 0 — chr1 11130528 11130777 466_105919_2475(MTOR)_40a 0 — chr1 11128854 11128951 466_105921_2475(MTOR)_42a 0 — chr1 11128453 11128552 466_105922_2475(MTOR)_43a 0 — chr1 11128003 11128126 466_105923_2475(MTOR)_44a 0 — chr1 11127623 11127806 466_105924_2475(MTOR)_45a 0 — chr1 11127009 11127144 466_105925_2475(MTOR)_46a 0 — chr1 11126621 11126796 466_105926_2475(MTOR)_47a 0 — chr1 11124497 11124633 466_105927_2475(MTOR)_48a 0 — chr1 11121245 11121368 466_105929_2475(MTOR)_50a 0 — chr1 11117003 11117086 466_105930_2475(MTOR)_51a 0 — chr5 56820391 56820816 465_99619_4214(MAP3K1)_3a 0 — chr5 56872824 56873005 465_99627_4214(MAP3K1)_11a 0 — chr5 56885931 56886063 465_99635_4214(MAP3K1)_19a 0 — chr5 56815573 56816055 465_99617_4214(MAP3K1)_1a 0 — chr5 56817055 56817116 465_99618_4214(MAP3K1)_2a 0 — chr5 56856599 56856750 465_99620_4214(MAP3K1)_4a 0 — chr5 56859714 56859915 465_99621_4214(MAP3K1)_5a 0 — chr5 56864733 56864934 465_99622_4214(MAP3K1)_6a 0 — chr5 56865339 56865456 465_99623_4214(MAP3K1)_7a 0 — chr5 56865828 56865977 465_99624_4214(MAP3K1)_8a 0 — chr5 56871909 56872031 465_99625_4214(MAP3K1)_9a 0 — chr5 56872640 56872722 465_99626_4214(MAP3K1)_10a 0 — chr5 56875031 56875310 465_99628_4214(MAP3K1)_12a 0 — chr5 56878979 56879101 465_99629_4214(MAP3K1)_13a 0 — chr5 56880710 56880802 465_99630_4214(MAP3K1)_14a 0 — chr5 56881082 56881272 465_99631_4214(MAP3K1)_15a 0 — chr5 56881569 56882866 465_99632_4214(MAP3K1)_16a 0 — chr5 56883526 56883679 465_99633_4214(MAP3K1)_17a 0 — chr17 12020886 12021001 465_99947_6416(MAP2K4)_1 0 — chr17 12032265 12032298 465_99948_6416(MAP2K4)_2 0 — chr17 12054888 12054991 465_99949_6416(MAP2K4)_3 0 — chr12 120978768 120979094 463_81838_6927(HNF1A)_1 0 — chr12 120999267 120999627 463_81845_6927(HNF1A)_8 0 — chr17 12069723 12069849 465_99950_6416(MAP2K4)_4 0 — chr17 12081355 12081530 465_99951_6416(MAP2K4)_5 0 — chr17 12095574 12095694 465_99952_6416(MAP2K4)_6 0 — chr17 12107789 12107909 465_99953_6416(MAP2K4)_7 0 — chr17 12113232 12113360 465_99955_6416(MAP2K4)_9 0 — chr17 12125293 12125371 465_99956_6416(MAP2K4)_10 0 — chr17 12129138 12129287 465_99957_6416(MAP2K4)_11 0 — chr17 12139838 12139884 465_99958_6416(MAP2K4)_12 0 — chr17 12141146 12141260 465_99959_6416(MAP2K4)_13 0 — chr20 56382984 56383176 427_16076_6790(AURKA)_7a 0 — chr20 56388155 56388197 427_16073_6790(AURKA)_4a 0 — chr20 56386256 56386533 427_16074_6790(AURKA)_5a 0 — chr20 56384269 56384324 427_16075_6790(AURKA)_6a 0 — chr20 56381432 56381571 427_16077_6790(AURKA)_8a 0 — chr20 56373407 56373556 427_16078_6790(AURKA)_9a 0 — chr20 56370484 56370659 427_16079_6790(AURKA)_10a 0 — chr20 56370157 56370340 427_16080_6790(AURKA)_11a 0 — chr3 142578645 142578704 427_14853_545(ATR)_1 0 — chr3 142568062 142568154 427_14854_545(ATR)_2 0 — chr3 142566120 142566261 427_14855_545(ATR)_3 0 — chr3 142562231 142563109 427_14856_545(ATR)_4 0 — chr3 142561242 142561421 427_14857_545(ATR)_5 0 — chr3 142560262 142560454 427_14858_545(ATR)_6 0 — chr3 142558623 142558776 427_14860_545(ATR)_8 0 — chr3 142556382 142556575 427_14861_545(ATR)_9 0 — chr20 58852980 58855333 462_70271_2778(GNAS)_3 0 — chr20 58905382 58905480 462_70279_2778(GNAS)_11 0 — chr20 58840106 58840886 462_70269_2778(GNAS)_1 0 — chr3 142555876 142556139 427_14862_545(ATR)_10 0 — chr3 142553824 142554015 427_14863_545(ATR)_11 0 — chr3 142553639 142553740 427_14864_545(ATR)_12 0 — chr3 142553226 142553398 427_14865_545(ATR)_13 0 — chr3 142549478 142549673 427_14867_545(ATR)_15 0 — chr3 142547724 142547910 427_14868_545(ATR)_16 0 — chr3 142542664 142542757 427_14869_545(ATR)_17 0 — chr3 142540903 142541034 427_14870_545(ATR)_18 0 — chr3 142536107 142536201 427_14872_545(ATR)_20 0 — chr3 142535079 142535205 427_14873_545(ATR)_21 0 — chr3 142523992 142524199 427_14874_545(ATR)_22 0 — chr3 142522727 142522841 427_14875_545(ATR)_23 0 — chr3 142519668 142519784 427_14876_545(ATR)_24 0 — chr3 142515394 142515515 427_14877_545(ATR)_25 0 — chr3 142512259 142512470 427_14879_545(ATR)_27 0 — chr3 142507930 142508109 427_14880_545(ATR)_28 0 — chr3 142505138 142505303 427_14881_545(ATR)_29 0 — chr3 142503361 142503453 427_14882_545(ATR)_30 0 — chr3 142499626 142499718 427_14883_545(ATR)_31 0 — chr3 142498596 142498774 427_14884_545(ATR)_32 0 — chr20 58841342 58841875 462_70270_2778(GNAS)_2 0 — chr20 58889124 58889353 462_70272_2778(GNAS)_4 0 — chr20 58891370 58891865 462_70273_2778(GNAS)_5 0 — chr20 58892109 58892209 462_70274_2778(GNAS)_6 0 — chr20 58895611 58895684 462_70275_2778(GNAS)_7 0 — chr20 58898940 58898985 462_70276_2778(GNAS)_8 0 — chr20 58903527 58903585 462_70277_2778(GNAS)_9 0 — chr20 58903671 58903791 462_70278_2778(GNAS)_10 0 — chr3 142497012 142497192 427_14885_545(ATR)_33 0 — chr3 142493131 142493311 427_14887_545(ATR)_35 0 — chr3 142485139 142485282 427_14888_545(ATR)_36 0 — chr3 142470085 142470183 427_14889_545(ATR)_37 0 — chr3 142469336 142469569 427_14890_545(ATR)_38 0 — chr3 142467933 142468068 427_14891_545(ATR)_39 0 — chr3 142466323 142466533 427_14892_545(ATR)_40 0 — chr3 142465096 142465240 427_14893_545(ATR)_41 0 — chr3 142459226 142459383 427_14895_545(ATR)_43 0 — chr3 142458957 142459111 427_14896_545(ATR)_44 0 — chr3 142457603 142457755 427_14897_545(ATR)_45 0 — chr3 142450465 142453233 427_14898_545(ATR)_46 0 — chr20 58909161 58909216 462_70280_2778(GNAS)_12 0 — chr20 58909349 58909423 462_70281_2778(GNAS)_13 0 — chr20 58909520 58909579 462_70282_2778(GNAS)_14 0 — chr20 58909683 58909804 462_70283_2778(GNAS)_15 0 — chr20 58909950 58910081 462_70284_2778(GNAS)_16 0 — chr20 58910333 58910401 462_70285_2778(GNAS)_17 0 — chr20 58910682 58910829 462_70286_2778(GNAS)_18 0 — chr3 142449428 142449602 427_14899_545(ATR)_47 0 — chr9 78031099 78031235 462_70175_2776(GNAQ)_1 0 — chr11 108251836 108252031 427_14221_472(ATM)_15 0 — chr9 77815615 77815770 462_70177_2776(GNAQ)_3 0 — chr9 77797519 77797648 462_70178_2776(GNAQ)_4 0 — chr9 77794462 77794592 462_70179_2776(GNAQ)_5 0 — chr9 77728513 77728667 462_70180_2776(GNAQ)_6 0 — chr9 77721322 77721513 462_70181_2776(GNAQ)_7 0 — chr19 3114943 3115072 462_70070_2767(GNA11)_4 0 — chr11 108268409 108268609 427_14228_472(ATM)_22 0 — chr11 108293312 108293477 427_14241_472(ATM)_35 0 — chr11 108310159 108310315 427_14249_472(ATM)_43 0 — chr11 108325309 108325544 427_14256_472(ATM)_50 0 — chr11 108333885 108333968 427_14264_472(ATM)_58 0 — chr11 108354810 108354874 427_14271_472(ATM)_65 0 — chr19 17841388 17841546 463_81750_3718(JAK3)_8a 0 — chr19 17834851 17835003 463_81758_3718(JAK3)_16a 0 — chr19 17826742 17826910 463_81766_3718(JAK3)_24a 0 — chr2 212538448 212538530 461_58772_2066(ERBB4)_1a 0 — chr2 211947429 211947616 461_58774_2066(ERBB4)_3a 0 — chr2 211788024 211788159 461_58775_2066(ERBB4)_4a 0 — chr2 211750638 211750704 461_58776_2066(ERBB4)_5a 0 — chr2 211725075 211725194 461_58777_2066(ERBB4)_6a 0 — chr2 211722392 211722534 461_58778_2066(ERBB4)_7a 0 — chr2 211713534 211713648 461_58779_2066(ERBB4)_8a 0 — chr2 211712049 211712176 461_58780_2066(ERBB4)_9a 0 — chr2 211705317 211705391 461_58781_2066(ERBB4)_10a 0 — chr2 211701966 211702166 461_58783_2066(ERBB4)_12a 0 — chr2 211679051 211679184 461_58784_2066(ERBB4)_13a 0 — chr2 211673163 211673257 461_58785_2066(ERBB4)_14a 0 — chr2 211665322 211665477 461_58786_2066(ERBB4)_15a 0 — chr2 211657949 211657994 461_58787_2066(ERBB4)_16a 0 — chr12 56093763 56093896 461_58756_2065(ERBB3)_13a 0 — chr12 56094401 56094556 461_58758_2065(ERBB3)_15a 0 — chr12 56095256 56095310 461_58759_2065(ERBB3)_16a 0 — chr12 56095664 56095806 461_58760_2065(ERBB3)_17a 0 — chr12 56096502 56096622 461_58761_2065(ERBB3)_18a 0 — chr12 56096747 56096846 461_58762_2065(ERBB3)_19a 0 — chr12 56097044 56097230 461_58763_2065(ERBB3)_20a 0 — chr12 56097784 56097940 461_58764_2065(ERBB3)_21a 0 — chr12 56098758 56098905 461_58766_2065(ERBB3)_23a 0 — chr7 55165279 55165437 431_48556_1956(EGFR)_16 0 — chr7 55170306 55171045 431_48558_1956(EGFR)_18 0 — chr7 55171174 55171213 431_48559_1956(EGFR)_19 0 — chr7 55172845 55172957 431_48560_1956(EGFR)_20 0 — chr7 55172982 55173124 431_48561_1956(EGFR)_21 0 — chr7 55173920 55174043 431_48562_1956(EGFR)_22 0 — chr7 55174721 55174820 431_48563_1956(EGFR)_23 0 — chr7 55181292 55181478 431_48564_1956(EGFR)_24 0 — chr7 55192765 55192841 431_48566_1956(EGFR)_26 0 — chr7 55198716 55198863 431_48567_1956(EGFR)_27 0 — chr7 55200315 55200413 431_48568_1956(EGFR)_28 0 — chr7 55201187 55201355 431_48569_1956(EGFR)_29 0 — chr7 55201734 55201782 431_48570_1956(EGFR)_30 0 — chr7 55202516 55202625 431_48571_1956(EGFR)_31 0 — chr7 55205255 55205617 431_48572_1956(EGFR)_32 0 — chr12 112446275 112446398 472_140050_5781(PTPN11)_2a 0 — chr12 112482073 112482205 472_140058_5781(PTPN11)_10a 0 — chr10 87952117 87952259 472_139791_5728(PTEN)_6 0 — chr1 11115395 11115468 466_105931_2475(MTOR)_52a 0 — chr1 11114812 11114887 466_105932_2475(MTOR)_53a 0 — chr1 11114317 11114453 466_105933_2475(MTOR)_54a 0 — chr1 11112851 11112917 466_105934_2475(MTOR)_55a 0 — chr1 11109289 11109370 466_105936_2475(MTOR)_57a 0 — chr1 11108180 11108286 466_105937_2475(MTOR)_58a 0 — chr1 11106604 11107500 466_105938_2475(MTOR)_59a 0 — chr19 3094651 3094787 462_70067_2767(GNA11)_1 0 — chr19 3110148 3110333 462_70068_2767(GNA11)_2 0 — chr19 3113329 3113484 462_70069_2767(GNA11)_3 0 — chr19 3118923 3119053 462_70071_2767(GNA11)_5 0 — chr11 108227624 108227696 427_14211_472(ATM)_5 0 — chr11 108227775 108227888 427_14212_472(ATM)_6 0 — chr19 3119205 3119359 462_70072_2767(GNA11)_6 0 — chr19 3120988 3121179 462_70073_2767(GNA11)_7 0 — chr11 108229177 108229323 427_14213_472(ATM)_7 0 — chr11 108243952 108244118 427_14215_472(ATM)_9 0 — chr11 108244787 108245026 427_14216_472(ATM)_10 0 — chr11 108246543 108246560 427_14217_472(ATM)_11 0 — chr11 108246963 108247127 427_14218_472(ATM)_12 0 — chr11 108248932 108249102 427_14219_472(ATM)_13 0 — chr11 108250700 108251072 427_14220_472(ATM)_14 0 — chr11 108252816 108252912 427_14222_472(ATM)_16 0 — chr11 108253813 108254039 427_14223_472(ATM)_17 0 — chr11 108256214 108256340 427_14224_472(ATM)_18 0 — chr11 108257480 108257606 427_14225_472(ATM)_19 0 — chr11 108258985 108259075 427_14226_472(ATM)_20 0 — chr11 108267170 108267342 427_14227_472(ATM)_21 0 — chr11 108271063 108271146 427_14229_472(ATM)_23 0 — chr11 108271250 108271406 427_14230_472(ATM)_24 0 — chr11 108272531 108272607 427_14231_472(ATM)_25 0 — chr11 108272721 108272852 427_14232_472(ATM)_26 0 — chr11 108279490 108279608 427_14233_472(ATM)_27 0 — chr11 108280994 108281168 427_14234_472(ATM)_28 0 — chr11 108282709 108282879 427_14235_472(ATM)_29 0 — chr11 108284226 108284473 427_14236_472(ATM)_30 0 — chr11 108287599 108287715 427_14237_472(ATM)_31 0 — chr11 108288976 108289103 427_14238_472(ATM)_32 0 — chr11 108289601 108289801 427_14239_472(ATM)_33 0 — chr11 108292618 108292793 427_14240_472(ATM)_34 0 — chr11 108294926 108295059 427_14242_472(ATM)_36 0 — chr11 108297286 108297382 427_14243_472(ATM)_37 0 — chr11 108299713 108299885 427_14244_472(ATM)_38 0 — chr11 108301647 108301789 427_14245_472(ATM)_39 0 — chr11 108302852 108303029 427_14246_472(ATM)_40 0 — chr11 108304674 108304852 427_14247_472(ATM)_41 0 — chr11 108307896 108307984 427_14248_472(ATM)_42 0 — chr11 108312410 108312498 427_14250_472(ATM)_44 0 — chr11 108315822 108315911 427_14251_472(ATM)_45 0 — chr11 108316010 108316113 427_14252_472(ATM)_46 0 — chr11 108317372 108317521 427_14253_472(ATM)_47 0 — chr11 108319953 108320058 427_14254_472(ATM)_48 0 — chr11 108321300 108321420 427_14255_472(ATM)_49 0 — chr11 108326057 108326225 427_14257_472(ATM)_51 0 — chr11 108327644 108327758 427_14258_472(ATM)_52 0 — chr11 108329020 108329238 427_14259_472(ATM)_53 0 — chr11 108330213 108330421 427_14260_472(ATM)_54 0 — chr11 108331443 108331557 427_14261_472(ATM)_55 0 — chr11 108331878 108332037 427_14262_472(ATM)_56 0 — chr11 108332761 108332900 427_14263_472(ATM)_57 0 — chr11 108334968 108335109 427_14265_472(ATM)_59 0 — chr11 108335844 108335961 427_14266_472(ATM)_60 0 — chr11 108343221 108343371 427_14267_472(ATM)_61 0 — chr11 108345742 108345908 427_14268_472(ATM)_62 0 — chr11 108347278 108347365 427_14269_472(ATM)_63 0 — chr11 108353765 108353880 427_14270_472(ATM)_64 0 — chr7 55143304 55143488 431_48544_1956(EGFR)_4 0 — chr7 55157662 55157753 431_48552_1956(EGFR)_12 0 — chr7 55168522 55168635 431_48557_1956(EGFR)_17 0 — chr7 55191718 55191874 431_48565_1956(EGFR)_25 0 — chr5 150086378 150086427 429_36453_1436(CSF1R)_2a 0 — chr5 150080766 150081024 429_36454_1436(CSF1R)_3a 0 — chr5 150080051 150080336 429_36455_1436(CSF1R)_4a 0 — chr5 150078111 150078248 429_36456_1436(CSF1R)_5a 0 — chr5 150077275 150077435 429_36457_1436(CSF1R)_6a 0 — chr5 150070455 150070571 429_36459_1436(CSF1R)_8a 0 — chr5 150070181 150070302 429_36460_1436(CSF1R)_9a 0 — chr5 150069872 150070063 429_36461_1436(CSF1R)_10a 0 — chr5 150068214 150068330 429_36462_1436(CSF1R)_11a 0 — chr5 150061722 150061849 429_36463_1436(CSF1R)_12a 0 — chr5 150061490 150061595 429_36464_1436(CSF1R)_13a 0 — chr5 150060861 150060972 429_36465_1436(CSF1R)_14a 0 — chr5 150057503 150057592 429_36467_1436(CSF1R)_16a 0 — chr5 150057286 150057384 429_36468_1436(CSF1R)_17a 0 — chr5 150056218 150056341 429_36469_1436(CSF1R)_18a 0 — chr5 150056025 150056137 429_36470_1436(CSF1R)_19a 0 — chr5 150055236 150055336 429_36471_1436(CSF1R)_20a 0 — chr5 150054321 150054430 429_36472_1436(CSF1R)_21a 0 — chr5 150054068 150054224 429_36473_1436(CSF1R)_22a 0 —

Supplementary Data 3

SEQ ID Sequence NO Name Sequence 1 632327_266823 TGGCATTAGGGACCCCAAATCCAGGTCTGCTCCCAGTGCCATAGGAA 54_Target2.1_1 GCAACCAGCCCCCAACCCCCACCTGCTCTTGGGAGCTGGCCCACAC CAGAAATGGACTGAGTAGACATGAGAA 2 632327_266823 CTGACCCCAGCTTCCACCAATGCCGTTAAGATGCCGCCACTTGGGTG 54_Target2.1_2 AGGGGCTCCTCCAGGTACTGCACCAAAGCCTGGGCCTGCAGAGGGA GAACAGAGATCAGTCCCGCACACAGCC 3 632327_266823 CCAAGACACATGACAGGAGTTGAAGTTTATTCTTGGAAAAAACAAAGT 54_Target2.1_3 CCCATCCTCCCCCCATTGTCTAAGAAGGTTCTTCTAGGAGGCCCCGC CCCTCCAAATGGTCATTTCTCTTTT 4 632327_266823 CTACTTTCTTGGATGGGAGGAATCAGAGAAGATAGGAAGAAGCAGGC 54_Target2.1_4 ATCGCTTCTAGGATTCCTCATGTTCTGCAAGGATGGACTTCTACCCAC CCCTTCACCATGACCTTCTGCGAAC 5 632327_266823 AATGGTTCTTGGCAGTTACGCCAAATAGTCCTTGTCCTCACCAATGG 54_Target2.1_5 CATGACCTCACCTAGACCCTGCTGCTCAGAACAGAGTCTTACCCACC TCATAGGCAAAACTGGGAGTGAGCTC 6 632327_266823 AGACCCTCTCAAAAAAATAAAAGGCACGCACGCCCCCAAACCTGAAA 54_Target2.1_6 TGATAGACACTAACCTCTCAGGGCCTTTATATTCTCTGTGCAACACAA CCCCCACCAGACCCTTGCACCTCT 7 632327_266823 TGTGTAAGCACATAAACACCTGGAAGAAGAAGAAAGGGATAGCTTGT 55_Target2.2_1 TCTAGGCTGTTAGGGGCACCCTCCCAACCCCAAGAATAGAAAAGGCA CTCACTGGCCAGTCGAAGTGGTTCAT 8 632327_266823 GTGTTTATGTGCTTACACAGACCCTCCCCAGATCTTGAAGCCCTTTGT 55_Target2.2_2 AGACAAGAGGCCTTTGCTGTGAGGCCTCAGGTCCTGTACAGGGAGT AGAAGTAACCCAGACCTCCCAAAGGC 9 632327_266823 ACCCAGACCTCCCAAAGGCCTTCATCTCCAGACCCTGCTCCTACACT 55_Target2.2_3 CAGACCACTCACCCCAGCTGTCTGTTTCTGCCCCAGGTCTCTGCCTA CCCAATATCCTTAAAGCAGGTCTGTA 10 632327_266823 TCCTTAAAGCAGGTCTGTATAGGGAGCTACCAGCCCCCTTCCCCAGT 55_Target2.2_4 GCCATATAAAGGAACCCATCCCAGAGAAGTGGGTAGGTTTCGAGTCC CAGCTCCACCCAAGATGAGAAACACT 11 632327_266823 ACCCAAGATGAGAAACACTGCCCATCCCAGGCCCTGGGCTGTCAAG 55_Target2.2_5 GAAGGGCAGAAGTTACTGTGGCCATGATACTCCCACAGCTCTGCATT GCAGGAGGGTGACTGGTGTTCTATCAG 12 632327_266823 GTGACTGGTGTTCTATCAGCCCCTGGTCTAATATCCCTTACTCTGGTT 55_Target2.2_6 CCCCCAGTGTACCCCCCTACCAGCTCTGAAGGAAAAGCAGGCCAAG TGGGTTTCTTCCTTTTTTTTTTTTTT 13 632327_266823 CACTGAGGGCTGAGTGTGCATTGCTGGGCTTCTGGAATCTGTGGTGA 56_Target2.3_1 GGGCCGGTCCCCCAACTAATGAGCAAGAAATAGCCCCTCAGAAACC CACTTGAGGCCAGGCGCGGTGGCTCAC 14 632327_266823 GTGGGCTGTCTCTGAAGGTGGTGTGGGTTTTTGGGTTGGGGGCGGGT 56_Target2.3_2 GGAGCTGCTTCTCCCGCTTGCGGGAGCCCAGGCTGAGAGCAGACAC CCAACCTGTCGAACCTGTCTGACGTCA 15 632327_266823 TCATCATCTCTCCACCCACCTGGGCCCCAGGTCTCCAGCCACCCCG 56_Target2.3_3 CTCTTCCTGTTCTCAGCTTCCGTCCTCTCTGCTTCCTTACAGCACCCC CACCTGCCAGAGCTGATCCTCCCTAG 16 632327_266823 GCTCAATGCCCTCAACCCTCAGCTCTCAAAAGATCTGGTCCTGCCCC 56_Target2.3_4 TCCTCTCATTGGGGGTAAGGGGACTTCTGCAGCCAGAGGGATTGGG GGCCAACTCAAGGTTAGGCAGGGCCTA 17 632327_266823 GAACCCAACTCACCCTTGAAGACAAAGTTATAATCTTCCTCAGTTCCA 56_Target2.3_5 TTCCCCATCTTGGCTCCGCATGGAGGGTGCAGGTGTCTTCGGGGAC AGAGGCGACAAATCTGTGTGTTGGCT 18 632327_266823 TTCTGAAGGAATGAGGAGCCCCAGGAGGTCTTGGTAAGAGATAAAAA 56_Target2.3_6 AACAGGAGGGGGCCCTCTCTGGCTCTATTCAATCTCTTTCTGGGTCT CTCAGGCTTCCTCTTGCTTCAGGGAA 19 632327_266823 TAACTCAGCACTCTTAAGGAGGAATCAACATCATTATTTACCACAGTA 56_Target2.3_7 GAGCATACTCAGAAGCTCCCTGACTTTTGCCCCTGCAACCAGACCCT CCCCCACTCCCTGCAGCTTTCTTTC 20 632327_266823 TTAGGCTCCTCTGCCCCGTTCCTAATAGAAACCCAAATCCCTGGTGT 56_Target2.3_8 CAGCCAGTGCAGCACAAGAGATGGAGGTCAGACTTCAGAAAGGACT TCCCTCTTTTATTTTTTTTTCTGAGA 21 632327_266823 ATGAGCCACCACACCCGGCCAGGACTTCTCTCTTGAGAAGAAAGGG 57_Target2.4_1 AAACCAGCAAACAAGAGGAAGAAAGTCATCTTTTCTGGGCAGGTGTA CAGGGAACGAGAGAAAGGAGAGACACA 22 632327_266823 CAGACGAGGCTACAACCCTAGGAGTCCTCTGGATTCTATCAGACTCT 57_Target2.4_2 GCAGCAAATTCATGATATTTTCTGTCTTCCCTATGTATTTATTGCCCCA CCCTATAATGGGATGTGTCTCTCC 23 632327_266823 AGCCTCGTCTGCCTGGCCCTTGGCTGACTCACTGGACCTGCATACCA 57_Target2.4_3 GGCACTGGGCTCAACTTTGCTGTCCCTGGAAGCATGCATGTATCTTT CTAGCCCCTGTGTTTGGTGCCTTTGC 24 632327_266823 GGTGCCTTTGCTGTTTTCCAACCCCACCTTCATACTTCCTTTAGGGCA 57_Target2.4_4 GGGTGGACTCTCCAGCCACCCTACCCCAATGCCTCTCCCAACCTCAG CCCGGCCCCTCCCTTGAGCTGGGAC 25 632327_266823 AATGGTAGTTCCTCATATTATTGCCCCAGACTATTGCTAACCCTTTCC 57_Target2.4_5 TTCCTGGAAAAGATGCCAGTAGTACAGGTTCCCCAGCTCAAGGGCG GGTTCTGGAGTGAGAGTCCCAGCTCA 26 632327_266823 TCCCCTACTGGGCACATCTCCCTCATCCCTCTCAGTGGGTGGGCTCT 58_Target2.5_1 CAGCCCTAGCGTCATACCACAAAGGTGCTTAGGGCAAGGGAATTGAA GTCAGACTTTGTGGCCTTTTGTAAAC 27 632327_266823 GTGTGTATATGTGTGTGTGTGTTCCTGCCTCTCCCCTACTGGGCACA 58_Target2.5_2 TCTCCCTCATCCCTCTCAGTGGGTGGGCTCTCAGCCCTAGCGTCATA CCACAAAGGTGCTTAGGGCAAGGGAA 28 632327_266823 CACACACGCATACACACACATCCTCTTACCCACACATATCCATATTAT 59_Target2.6_1 TTCCAGCTTTTCCATACTGTCCTATGCAAATAAGGAATGTTTAAATATA TATTTTTTATTTTTATTTTTTGA 29 632327_266823 CCAGGACCAAGTGGGGTGATCAGGACCCCTCCAGGTGGGTCCCGG 60_Target4.1_1 GTGCGGATGGCCAGTTGGGCGCATGCTTATTGGGCCTGCATCCGTT GGCCACGGAGGCTCTTTGGGACAAGCAAA 30 632327_266823 GGCCACCCTGTTGTTGTGGGAGTATTAGGGGAAGTTGCCACTAAGG 60_Target4.1_2 CTGGCAGGTCCTGGAGTTCCACCCAGGATGGGGACATGGGGGAGG GAAGAGGAGGTGCCCCTCAGAGCCTGAGG 31 632327_266823 GGATAGGAGCCATGCTCCCCTGGGGTGGCTCTGGAACGTGGGCCCC 60_Target4.1_3 GTGCACAGGCTATGTAGTCTGCTCACACCCTTGCTGCCTGCCACCCG GGCACCCAGGACTTGAGCCCAGACCCT 32 632327_266823 GCCACCCCACAGGTGGCTTTTTATTCCCTCCTGCTGCTGAGTGTCAC 60_Target4.1_4 GCGTGGGGCTGAGGGCCTGCACGCCTTCCCGGCCTCATCCTCTCCG ACGATTCACGCCCTCCTAAGGCTGGCA 33 632327_266823 CACTGCCAAGGGCTCCCCGACACAAGCACAGAGCACAGCCTGGCCT 60_Target4.1_5 TGGCTGCAGCACCACAGCAGATGCCTTTATGCCCAGGGCCAGCTAT GGGCTGAAAGCACACCCCAGTCCTCACT 34 632327_266823 TCCGCACTGTCTGTGGGGTGTTTTGGGTTGCAGGTTCCATGTCCTGA 60_Target4.1_6 AGCAGGAGAGCCCTCCCCATGCCACCTCCTCTGCCCAGCCTCTTAG GGACAGTGCCTGGGATGCCCTGGCTGG 35 632327_266823 CAGCCTCACACCGAGCTCTCTGCCAAAACCCCGGATCACAAGCATGA 60_Target4.1_7 GCTCCAGCAGGTCCGCTTGAGTGAACACCGCTGATCCTGCCTGCAG GGGTATAGGCCTGGGGCCTGCCAGCCG 36 632327_266823 TTCTAGCCTGGGGCAGAAGTAGGGTGGAGGGGTGGGTCTAGCCTCC 60_Target4.1_8 TTGATGACACAGTTGGGGTTGGAGGTGGGGGCTACCCCTATTCTGG GCCTGGTGCTGTCCCTGAAGTCAGGGGT 37 632327_266823 TGTAGAGGTGGGAGGAAGTCAGGGAAGCAAGACACAGGTGGAGCCA 60_Target4.1_9 GGGCCTCTCCTGTGCTCGGAGGGCCAGGAAGGGCCTGACAGAGGG CAGAGCCCCACCCTCTTACACGGAGACCA 38 632327_266823 AGGAGGCAGTTTTGGAGTCAGAGGTGAAGTGTGGGGAGTGGGATTG 60_Target4.1_10 GGTGATAGGGAAGTTTCTCCAGCAAAGACACTGGGCAAGCCTCTTCC TTGGCCCCCAGATAAAGGGCTGCAGGG 39 632327_266823 CCCTTTTCTTCTGAGCCTGGACAACTCCTTCCCTTGCCCCCAGGAGC 60_Target4.1_11 CCACAGCCGGCTAAACCAACTGGTCAGCTAGAACCAACCAGCAGGG GAGGTGCGCTCCAGGGGGGCTTCTAAG 40 632327_266823 TGGTAGGACCTCCTAAAGGGACAGCAGATGCCAGGAGAGGGCCGCA 60_Target4.1_12 AAGGCACAGCGTTGGAACCAGAGGGTTCCTACCAAGTTGACAACTCC AAAAGAGCATGGTGGTCCCCCAAGGAC 41 632327_266823 ACAGAGAGACAGTCAGTTGTCCTCAGAATTGGATCCAGAACCTCGTC 60_Target4.1_13 TTCTGGCATGGCCCCCCAGTGCAGCACCACATGTGGCCTCCGAATTC CCAGTCTGGGATTGGGGGAGCTCTG 42 632327_266823 TGGCCCCAGGTCTAGGCGAGGGATGGAAATAAGGACAGTGCCACTA 61_Target4.2_1 GGGCCTCCTGTCTGTACAGGAGGGGCCCTGAGACAGCTCCTCAAAC CCCTTTCCCATTATACGGATGGTGCAGA 43 632327_266823 GGCCATGGTACCAGTACACAGTGCTCACCCTCCTGCTCAGACAAACA 61_Target4.2_2 GTAACGGCCAGAAGCTCCAAGCCTCCTGCCCCAGCCCAAGGTGACT TTCCTGGCAGAACCTGGGACTGCCCTG 44 632327_266823 CCCTGCCCTGCCCTGCCTCCACCCAGCTCCCGGGCAAGCAGTGCCA 61_Target4.2_3 GGAGGAAGTGTCAGCAGCTCCTCCCCAAAGCTCTTTTCCCCACAGCC CCGCCACCCCCGTACCTGGGCCCCGAT 45 632327_266823 CCCATCGCCCTGGGCCGGGACACGCCCCCTCTTGTGCCCATTCCTT 61_Target4.2_4 TCCCTCGGTGGAGAGTTGGGTGGTGGGGGCTGGCCGGCCTGTGAG AGCAGGTGTCGGGGTGCCTGGAGAATCGG 46 632327_266823 TCCCTCCTGAGAGTCCCTGGTTTCCTTTCCCACACCCCTCCCGGGGC 61_Target4.2_5 CCGCCGCAGCTTTGGTCACCTTCTCAGAATGACCATGGGTTGATCTC TTCTTTGCTAGTGAGATGTTTCCCAT 47 632327_266823 AGGGAACGGGAGCCTTGTGGTAGAAAAGGAGCTGCTGTCCCCGATC 61_Target4.2_6 TGGAACTCGAAACCCCAACATCTTCCAGGCCGTAAGCCCCTCACCCC GCACCCCTAGGCAAATCTCCGCTTTCC 48 632327_266823 TTTCCCAACTCCCTCACCTCGGTCCAGCGATCAGCCTCTCGGACCCT 61_Target4.2_7 CGAGAGGGAGCTCCGACCCTGCTCTAGCTCTTGCGGGTCCCCCAAC CATGGACTCCAAAGCCTTCATGTCCAC 49 632327_266823 CGCCGCGGGCTTTGCAGCCCCGCACGCCGAGCGCCGGTGGAAGCC 61_Target4.2_8 GGGTCCTGGCCACAGGAGTCCTAGCCGCACGCGAGTGTCGCGGGA GGGGGCCAGGGCCGGGTTCTGCAGTGTGGA 50 632327_266823 CGGCGCGCCCGCCCCCACTCCCGCTCCGCTCCCGGAACCCCGCGC 61_Target4.2_9 CGGCGGCCGGAGTGAATCATTAACTGGAGCCGGGTGCTCCGGCTGC GCAGCCTTCCCCGCTGGCGCCACGCACTT 51 632327_266823 CACTTGCCCGCCCGGCCTCGGTCCCCCGGAGCTCCTCCCTCTCCGG 61_Target4.2_10 GAGCCGGTGGGCAGTCCCCACGCCACACCAGCCGGACCACCCGCC AGAGGCTCAACGGCCCCTCCTCGCAG 52 632327_266823 GCGTTGGCGGGGCCGGGCGCGGGGGCCGCCAGCCGGTAGGAGGG 62_Target4.3_1 TTCCTGTGTCGGGAAAGTGGCTGGCGGGGCCCGCGCTCCCCGGCC GACGGCCGCCTGCTGTGTCACCTTGGGCCTC 53 632327_266823 GGCCCCGCCAACGCACCCGAGGCGCACAGGCTCCGGAGCCCCCGC 62_Target4.3_2 GGTTCCTGCCTCCCGGCTTCCCGGCCAGGGCAGAAGGAGATCCCAG GGCCGCGGACCCCGGCCGGCGGTTCCCAG 54 632327_266823 CCGGCGGTTCCCAGGCCCCGCAGGTCCGGCAGGAAATGCCGCTCG 62_Target4.3_3 CTTAACCCCTTCCAGCCCGCTGCCGCCTCCAAGCCCGTACGCGGCC CGGCCCCACCTGGCGCCCTCACCAGGTGG 55 632327_266823 ACCGGGGCGGCTGCGGCGCGCTCGGAGCCCCGAGGGCACGCGGC 62_Target4.3_4 CCGGGCAGCTCGGTGTGCGCCCCCGCGAGAGCCGGGGCCCCAGGC CCGCCGGACACCATGAACCACCTGGTGAGGG 56 632327_266823 GCAGCCGCCCCGGTGCCGCCGCGCAGCTGCCGCCTCGGCCACCCA 62_Target4.3_5 GAGCCGGTCCAGCCGCTCTCCGCCTGCCGCCACGGCCCAGCCGGC CCAGCCCGATCCCAGCATGCCCGGCCGCGC 57 632327_266823 GGGGGCGGGGCGGGGGGCGGCCCCTACTGGGCGGGCTTCTGTCT 62_Target4.3_6 GCGCGCCCGCGCCCCCGACAGGCGGCTTATTTGCATGGAGAGCGG CGGCGGCCAATGGGCGCGCGCGGCCGGGCAT 58 632327_266823 GAGGCTCCAGGCCCCTGCCCGAGGCCAGGCTTCCAGCCTAGGGCG 63_Target4.4_1 CAGGACACCGCTCTCCAACAAATGCACGTCCCCGCCTTCCACCCAG GCGAGAACGCACCGAAGGCCTACGCAAAC 59 632327_266823 ACGCAAACTCCTCCACTTCTGGGAAGGCTGCCCGGTTTGCCTTCTTC 63_Target4.4_2 CTCCAGAGCCGAGACATGGCCTCAAGTCGACTTGTCTTTCCCGCTAA CCAACCCCAGGGCATTCATCGCGTGT 60 632327_266823 GGTGGGACCGTCTACAGTCGGAGCTGTGGTGGTGATGATTCGTCTC 63_Target4.4_3 CTACAGGCTGGGGCACGCCCCCTCCCCTTTCCCTCTAGATTCAGATT TGAGTCCCACGGCCCATGGACACGCGA 61 632327_266823 TCCCCAGATGTCGGCACAATGCAGGGGAAGGTAGGTGCTGCCCGTG 63_Target4.4_4 AAAAGCGCTGGGTCGAGAGCTCGCCAGCCTCCCTGCTTGAGGCTTC ATTTCCTGGGGTCCTTACACGGTGGGAC 62 632327_266823 GCTGAAGCAGATGAGTTGGAGCAGGACTCAGGAGGGTACTAGGCCC 63_Target4.4_5 AGGTTTTAGGCTGAACCTAGGAATGAGTAATGAGAGGAGGCAGATCA GCTGGAGGACCAGCCCGAGTCCCCAGA 63 632327_266823 ACCGAGCAAGGGGCAACTCAGGAGAGCCAAGGTTGTCTCCACTCGG 63_Target4.4_6 TTTCCCCCGAGTGATTCTTCCTTCTATCTCCCTCATTCCCCCAGTGCC GCTCTCCTACCCCATGTCGCTGAAGC 64 632327_266823 TGCTCGGTTGCAGGTCAGTGACTGTCACCCCATGCAGCAGAACCAG 63_Target4.4_7 GGTGCCAGAGCCCCTGGGCCAGGCCAGGGAGGCACAATCTGCAGG GAGATGATAGGACCGAGCCTGGTCCAGAC 65 632327_266823 CTCTGCTGCGTGAAGCCGGGTCTACCCCGCTGCTTCCCTGCCACCA 63_Target4.4_8 GGGCTGCCTCGTGGCATCCCATTGCTCAGCCAGTGGCCCAGGATTG TTGACTGAGGGTCCTGTCTGGTCTGGAC 66 632327_266823 CAGCAGAGAATTCTCAAGCATGGCCTATGGAAGACACAAGCCCAGGT 63_Target4.4_9 GGGCCTGCAGCTGCCCCTCTGTCTGACCCCCAGGGCTCAGCCTACG CAGCGCCTGGCCAGATGTGCCACCTTG 67 632327_266823 AGACTCCTGTGTCCCACCCCTCCCAAAAAACTGGACGTCTGCATTTC 64_Target4.5_1 TTCAATATTTGGCTTGGGAAGCATTGGCCAGAACTCACAGCACAGCG GGTGAGGAAGGAGCAGTGGGATGAGA 68 632327_266823 GACAGAGCATGACCCAGAGTCCTCAGGAGGAACAGAACAGCTAGCC 64_Target4.5_2 AACACCCTGTGCCTCCCCGACACAGCCCGCCTCGCCTCAGAAGAGG AGCCAGCCTTCAGGGAAGCTGCCTGGAG 69 632327_266823 AGCATCTCCTCCTGCTTGTTCCCAAGAGCTGTGCCGGGCCCCTCCTG 64_Target4.5_3 CACCCTGACCCTGTCCAGCCACCCACTCCTCAGCCTGGCTGGCACA CCAGCTTCCCAGAGAGCAGGTCTGAAC 70 632327_266823 GCAGAGACTGCTGCCTGGGGCCCTGCCAGCAGGGCACTGCCTGCC 64_Target4.5_4 CATGAGGCCTGGTCTCCCCTCCCCACAGAAGTGGAGGCCCAGGGAT GACCTCAGGCTCCTGAGGGTCCCGCTGGT 71 632327_266823 TCATCCCCCAAGGTTCCAGCCATCCACCTCCTCTCTGCACCGCCCTC 64_Target4.5_5 CTTGGCCAACTAGGATGGAGCAGGGGCCAGCTCCCTTGAGGGCCAG GCCTTTTGTGTCCTTGCCCGTCCCTGC 72 632327_266823 AAAAGGAGCAAATTTTTGAAATGCCTGTGTCGGAGCCTGTTTCCCTTG 64_Target4.5_6 CTGCCTCCTGCTCACACCAGCAGCCCCACCCCCAGTGCTGTTCTAAT GCAGCTACTGGGGGAGGAGGGTCTC 73 632327_266823 CCCCACCCCCCAGCTACATCCCCATCAACACTGTGGGGCTTAACTTC 64_Target4.5_7 TGGGGCCTTGTTTCCAAAGCGGAAATGCCATTCTGGGAGGCACAGG CTTTTGGGGGAGGGAATTTAAGTGGAA 74 632327_266823 GGGTATGTGGGGCTGCATCCCTGTCCTTGACAGCGGAGGTCCGGGA 64_Target4.5_8 GGCTGGACTGGGGGTGGGGTGAGGTTCTGCCCCCATATACCCCGGC CAGAGCCTGGCCAGTGGGTGCTCCTCCC 75 632327_266823 TCTCAAAAAAAAAAAAAATTGGGGCTAACGGTGAGCCTGTTTTGCAG 64_Target4.5_9 GATTGCTGTGTGCACAAAATAAATGCATGGGCATAGGGCCCCTGGCA CTGGCTGGGCGCAGAGGCTGTGCTGG 76 632327_266823 TTTCTTCCCTGGCCCTGTCCCTTCTGTGCCCCGAAATGTGTGGGATG 65_Target4.6_1 GGGCAGTGGTTGGTAAACTGGGTCTCGGTCTCTTCATGTGAAAAATG GGGCTAGGCTGGGTGCAGTGGCTCAC 77 632327_266823 GCCTGTCCTTTTGCAGTCTGAGTGTGACAGGGGTGTTTGGCTTTCTG 65_Target4.6_2 AGCCTGGAGTGCTGCTGTCCCTGTCCCTAGATTCCCTTCCTGCTGCA GGGTGGGCTGAGGTCTAGCAGCCCCA 73 632327_266823 TCAACAAATGTTTACTGCACCCCTTCTCACCAATGGGGCTAAACTTAG 65_Target4.6_3 TGGGGTGGGGGTGGTGCTGGCCCCAGTGCTGAGCTCAGTTTTACTG GGGAGGAAGGTGCTTAGGTCTCAGTT 79 632327_266823 GTGTGTGCCTCTGCACTTAGGCGTGACTTAACCACCCCCATCCTCCA 65_Target4.6_4 GACTGGGGCAGCCTCAGATTTCTTCACCCAGGCCAGCCTATCCCATG AGGGCCACCTCTGAGGTCCCACCCAG 80 632327_266823 GACCATTGAGGAGAGCTGGTGGTCACTCTGCAGAGCGTCCCTCCGT 66_Target1.1_1 GGGGATGGTCCTGGGTGGCCTCAGGACTCAATGGAGGGAGTCCCG GGCGTGGCGTGTGTCTGTCTCAGGCCCCC 81 632327_266823 GCCCCCTGAGTATCACCAGCCACCCTTTGCTGGGTCCTGGGTACACA 66_Target1.1_2 AGCCACCCATCTTCAGATGTCAGGGTCTCCTCCAGCGGGCGCAGTC CCTCTGCCCTCCCTCAGCCCTTGGGAC 82 632327_266823 TCCCTCCCCCGGCCTCCCTCCCCCAGCTTCCCTAAATTCTGTCCTCT 66_Target1.1_3 TGCTCAACCCTCCAGGCTGTGATCGAAGCCAGGGCGCGAAAGTTGA TTCCAAATGGCCCCCTCTGCCCCAGCC 83 632327_266823 AGAGAAGCACTGAATGAACTTGGAGGCCAAAAAGAAAAAAAGCTTTT 67_Target1.2_1 TAACGTTTCATTTGGAAAGGATTTCACGCTTACAGAAGTCCAAAGGGT CCAAACTCCCTCCCCGCTCCCCAAA 84 632327_266823 TTTTCTTTTTGGCCTCCAAGTTCATTCAGTGCTTCTCTCCATTTCACTG 67_Target1.2_2 TAGGTTTAAACCGTTCAGTTATAAATAAATAATTTTATCCTCTGTCCTC GGCTTTCCCCCGTTTCCGGCAC 85 632327_266823 GACTTGGAGGGAGCTCCTGGCAGGGCCCTGCAGTGCCCAGGATGG 67_Target1.2_3 CCCCGCCGCAGAGACAAATCCAGCCCCCATGTCTGCAGTGCCGGAA ACGGGGGAAAGCCGAGGACAGAGGATAAA 86 632327_266823 AGAATCACCCCAGGGTTAGAGGATTCCACAGACCCCAAGAGACTCTG 68_Target1.3_1 AGTCCCATGATCCTCTGCCCTGCTGAGGTCCCAGGAGGCTGCACAC ATTGAAATCCACACCCTGAGTGGGAGG 87 632327_266823 TCCCGATGGGGCGTACGGCATAAACCCGGGGGACCCCAGCTCCCG 68_Target1.3_2 GGACTCGCCTCCTCTCTCCCTCCCACTCAGGGTGTGGATTTCAATGT GTGCAGCCTCCTGGGACCTCAGCAGGGC 88 632327_266823 AAATAAAAATAAAAAATAAAAAATCCAGTCTGCCCCCTGCTCACACCG 68_Target1.3_3 GACACCAGAATAAACTCCCGATGGGGCGTACGGCATAAACCCGGGG GACCCCAGCTCCCGGGACTCGCCTCC 89 632327_266823 CAGGGCCCCACCACGAGTGCCCTCAGTGCCTCACCTGAGGCCCCAG 69_Target1.4_1 CGAACATCCTCCTGCCAGTTTTGTCTGGGGGTTTTCTTCCCCCTTTAA GGCCAGGATTCTCAATCAAGAGGTGA 90 632327_266823 GAGGTCCCTGTGGCCCCAGCAAAGCCGGCCGTGGCAGGTGTGTCC 69_Target1.4_2 CGTGGGTGGGTGAGCTGGAAACGGACAGACAGCAGGACGTAGCAG GGGACAGGATGCAGAGCTCGGGAAGGCAGG 91 632327_266823 CCTCGTCAGGGAGGCGTCTCCTTGTGGGTGGCACGTGGGCATGTGT 69_Target1.4_3 TGCTCTGAGGGCTGTGGCCATGTTGCCCACCTGGCCAGGGACCCCC GACTTGGGTGGGTGACAGCCAGCCTCCC 92 632327_266823 CAATGCCCAGGCTGGGTCCCCACTTCCTCCTTTTGCCTTGGGAGCCT 69_Target1.4_4 GGGAGTCAGAACGGACTCCGGGGAGGAGGTGGGGGCTTTGGGCTC AAGGTCCCAACCTTTGTGGGGGCGGGGA 93 632327_266823 ATTGGGCAACTCAACGGCCTCTGGCATTGGGCTATAAGAGGAGCTTG 69_Target1.4_5 ACCGTGGGTGCACCCTGGACCCCACCATGGCTCACCGGCCCCCCAG CCCTGCCCTGGCGTCCGTGCTGCTGGC 94 632327_266823 CCCAGCTGTGCCAGAAGGGCTTTGGATGGACCTCGTGGTGGATATTT 69_Target1.4_6 CCCCACAATCCACCGGGGCCTGGAGGCTGGATGGATGGGCACGTG GCTCACTCACCGCTCAGCAGCAAGGCCA 95 632327_266823 ACAGATAGGCAACTGAGTCAAATGGCCAGGGCTCCCCCTTGCCCTTG 69_Target1.4_7 TCCTCCCCACCCCTGCAAGCGTTGGTCCCGAGCAGTGAGTGGAGTC TCCCCTGACCCTGCCTCAGTTTCCCCA 96 632327_266823 GCAAATGCTCAGTGAATATGCATGAATGAATGAATGAGTGAATGAATG 70_Target1.5_1 AGTGAGTGAGTGAATGAGTGAACAAATGAATGAGTGAATGAATCAAT GAGTGAGTGAATGAATGAGTGAATG 97 632327_266823 AGTGAATGAGTGAACGAATGAATGAGTGAATGAATCAATGAGTGAGT 70_Target1.5_2 GAATGAATGAGTGAATGAGTGAATGAATGAGTGAATGAGTGAATGAG TGAACGAATGAATGAGTGAATGAATG 98 632327_266823 AAAAAAGAAAAAGAAAAAGAAAATCACCCTCAGGATAGGGACCTGAG 70_Target1.5_3 GGGGCCCATGCTCTCTTCTTCCCCTGATTCCAGCATCACTAACTCCT CGACCCTTTCACTCACTCACTCATT 99 632327_266823 GTGAGCCACTGCACCCAGCCACCTGGTCTGCGTCTTAAAAGCCTTCC 71_Target1.6_1 TGACTCTCAGGACTGAAAGCTGCCACCAGGGCGCCTTTGGAAATCGT CGTAATTATAACCCCCCCGGCCTGGG 100 632327_266823 GGGAGCCCCCAGGCTGCAGGGAAAGGGGGGATGGCAGAGCAGCCC 71_Target1.6_2 CTGGGCCTCTCCGAGCCTCCGTCTCCCGATCTGCAACCCGGTCAGT GCCTGCTGGCTGGTGGGAAGGACTCAGCG 101 632327_266823 GCCCGGGTTCCCCCGCATCTGCAGGGAGGCCATGTAGGGCCGGGA 71_Target1.6_3 GTGTGGCTGCGCCTCGTGCCCGCCCACGATCTCCGCAGCTCGGGCA GCACCTGCAGGGGGGGAGTCCAGGCGTCA 102 632327_266823 AGCCACTTCTGCGGAGGCACCTTGATCCACCCCAGCTTCGTGCTGAC 71_Target1.6_4 GGCCGCGCACTGCCTGCGGGACATGTGAGCGGCCGCCTCCACACC CCTGTCCGCCCGCCCCGCCCTCTTCCTC 103 632327_266823 CTCGGCGACCCTGCCCCGGGCCTCCCCCCAGAACTGCCCACGCGC 71_Target1.6_5 GCGGGGCCTGGGGTCTGCAGACGGGGCTTAGCTGGGTCCTCCCCG GGCAGAGGGACAGTGGCCGGGCCAGGGCTG 104 632327_266823 CCACGTTCACCAGGCGCTGGGGTCTGCGGGGGTGGGGTGGTCACT 71_Target1.6_6 CCTCGGCGCCCTGGACACTCGCCGCCGCCCACAGCCGGCCCTTCC CGAGGCCGCGGTGCAGCCCCAGACCCCTCC 105 632327_266823 TGCTCGGAGCCCACAACGTGCGGACGCAGGAGCCCACCCAGCAGC 71_Target1.6_7 ACTTCTCGGTGGCTCAGGTGTTTCTGAACAACTACGACGCGGAGAAC AAACTGAACGACGTTCTCCTCATCCAGG 106 632327_266823 CCATTTCTGTCTCCATAGAGTGGGGACAGCCCCCCATTTCCCCATGA 72_Target7.1_1 CACACATGAGATACTAAAGAGGTGCCCTACAAAGTCCCATCACCACT AGATGATTTTTTTTTTTTTTTTTTTG 107 632327_266823 GAGTTGGGGCTCCGCGGTGGCGGTCAGCAGCATAGGCCCAGGTCC 72_Target7.1_2 CATGTGACCCAAGGCTGTCTCTGAACCTCCATTTCTGTCTCCATAGA GTGGGGACAGCCCCCCATTTCCCCATGA 108 632327_266823 TCCCCCCCTTATGACCTGTAAACCCAGTTTCTGGCGGCCAAGGATGG 72_Target7.1_3 GGAGACAGGAGGCAACTGCTTGAGCGGAGTTGGGGCTCCGCGGTG GCGGTCAGCAGCATAGGCCCAGGTCCCA 109 632327_266823 CTGCCCCTCCACTCCCGACTATGAGAACATGTTTGTGGGCCAGCCAG 73_Target7.2_1 CAGCCGAGCACCAGTGGGATGAACAAGGGTAAGTAAGCCACTGAGA CACCTGCCAAAGTGGTGAATAATAAGG 110 632327_266823 CCGGGAGCTGAACAAACCCTGGGCTGCTCAGGATGGGCCCAAGCCC 73_Target7.2_2 GGTTTAGGCTTGCAGCCACGGTACGGCAGCCGGAGCGCCCCCAAGC CCCAAGTGGCCGTGCCATCCTGCCCCTC 111 632327_266823 AGCTCCCGGCTTCTGGCCACTCGGCATCGCCAGAGTCTCCAGGCCA 73_Target7.2_3 GCACAGGGCCAGCGATGGCAAGTCCAAGAAGCAGGCACCCGCTGAC CACCACTGCCCCGATAGTTGCAGAGGCC 112 632327_266823 CGACATCCGCCGAGACAACTGCTCTGGCCAGAAGCCTCTGCTCTGC 73_Target7.2_4 TGGGACACAACCAGCTCCCAGCACAACCTCTCTGCCTTCCTGGAGGT CAGCTGCGCCCCTGGCCTGGCCTCTGC 113 632327_266823 TGAGGTCCTGAACGTGCTACGCAACCCCTTGTCTCGTGTGGATGGG 73_Target7.2_5 GCGCTGGCCGCCCGCTGTGACCTTGACCTGCAGGCCGACTGCAACT GTGCCCTGGAGTCCTGGCACGACATCCG 114 632327_266823 AGGACCTCAAGCTTCTGCAGGTGGGCAAAGAAGGTCACTGGAAGCT 73_Target7.2_6 CTCGCAGGCCGTTCCCAGACAGGTCAAGGAGAATCACGTTGCTGGC CCGCAGAGACTGGTTGTGAGGCAGGCTC 115 632327_266823 GGCAGGCTCAGGCTGAGGCCACTGAAATTCAGGCACGTGGCACTGA 73_Target7.2_7 ACTCCGCGTTCCAGTCCACATCCGCGGAGGACACGGTGCACGACGG TTCTAGGCTGTCTGACTCCCGCAGCAGC 116 632327_266823 CGCAGCAGCAGCGGCAACAGCAGCGTCCATGCCAGGGTGCCCCCC 73_Target7.2_8 ATTCAAGCAACCTACGTAGAGACACCGGAATCCTAGCCCTGACCTCA GCCCTGTGGTCGCCCTCGCCTCCACCGC 117 632327_266823 CTCCACCGCCAGTGTTTATTATTATAGCTCAGACCAGCTCAAGCCGC 73_Target7.2_9 TTCTGAAATGGTAAAACGCAGCCCCAGTCTGGTCGCCTCCTTTGGCT GGTGGGCTGCCTCAGTCTCCCCTTCT 118 632327_266823 GCATAGGGTCCCGTCCTGGCCAACGAGGGCGCCCCAAATGTTCAGG 74_Target7.3_1 ACATAGAAGAAGGGGTTAACTGGCCCGGATCTCCTCCTCGCCTTCCA AGCCCGCTAAGCACTGGGGTTATCTAC 119 632327_266823 GCCCCCACTCCACCCTATCCCAGGACTTCCCAGCGACCCGCCGTTC 74_Target7.3_2 TGGGAGATACCGGGAGCGTGATCAGGGGGCGGGGCCGTTTCCAAG GCAACCGCTTATTTGCATAGGGTCCCGTC 120 632327_266823 GCAGAGGCAAAAGCGTGGCAGTGGGACCCAAAAGGTAGGACTGAGG 74_Target7.3_3 CTCTAGAACTTGCACCTGTGCAGGGACTGCAAACCAGACCTGGGAG GACCCTTTCAGCAGCCCCCACTCCACCC 121 632327_266823 AGCGACCCCAGCAGCGCTGCGGACGGTGCTGGCCGTGGCCGCTGC 74_Target7.3_4 GGCCCCCGTGTCCAGGTGGGCCAGGACGCAGCCTCTGGGCGCCGT CGCTTTTCCAGCATCGCAGAGGCAAAAGCG 122 632327_266823 CCTGCAAGGGGGCGGATCTCTGTCTTCATTCTTCCCCTCTGCACTCC 74_Target7.3_5 ACCCAGACACCAGTTCCTCTTCCCCCTGAGTCGCTGGGTGCAGAGC CAGAGGAACGCCAGCGACCCCAGCAGC 123 632327_266823 GCTAATAGAGGACATGAAGTCACTGGGTTCTAGCAAGAGGGAAGCG 74_Target7.3_6 GGACTCTGGTCCACCCCTCCCTCTTGCCCTCCATCCACCTCTGGTGA GAACCTTGAGGCCCTGCAAGGGGGCGG 124 632327_266823 ATGTCCTCTATTAGCACCCCAACCGACTGCCACCTCATCAACTCGCTT 74_Target7.3_7 CTTGATCTCAGCTTGGCTGGTTCCCAGCTCATGCAGTCATTTATTCAT TCAACAAGCATCACCCACGCTGGG 125 632327_266823 CCCTCCTCACTGTCCCCTCCAGCATAGAGGTGCCACTGTGCAAGAAC 75_Target7.4_1 TCAGTGGGAGAGGCTTGGAGGAGCTTGGAGAGCCAATGATAGGTTT GGGGAATCTTAGTGAACTCCTACTCAT 126 632327_266823 GGCTCCACATGGACCTCTTCCCCCACCACCAATTCCTTCTATCCTCTC 75_Target7.4_2 CACTCCTAACCATGCTATCCCAGCCAGCTACATTTTCCCAAGCTGCT GGGAGCCCTCCTCACTGTCCCCTCC 127 632327_266823 CTGGGACCTCAGCCTCCTCCCCAAGTTGCCCACCCCAGACACCAGG 75_Target7.4_3 CTCACTCCAGAGGGACTTCTTGAGCCAGTGCCCCTCTGCCCACGCA CCTGCCTTGGCTCCACATGGACCTCTTC 128 632327_266823 TGACACCAGGTTCAGGTGAGGCCTTCTCCCAGCCCACCCCTCCTCA 75_Target7.4_4 GTATCATTTTTGTCACTACTACCCCTCCAGTCTGCCTCAGGCCCCCAT CTGCTTCTGGGACCTCAGCCTCCTCC 129 632327_266823 CTCACCTGAACCTGGTGTCAGGTGGACCAGGTACAACCTATGCCAGC 75_Target7.4_5 CCGACTCACTGTGCCACCTTAACTGCGTGTGACACCATGTCCACAGC TGTCAAATGCACAGAGGCTTCTCCGG 130 632327_266823 ATGCACAGAGGCTTCTCCGGGATCTGGGAGGCTGGGAGTCCACTCC 75_Target7.4_6 CCCACGTTTTCCCCTCTTTTCGGCCTCTGTCCTTCACATCGCCAAACT CCAAGAAATGGTCAAAGGCTTTGAA 131 632327_266823 CGTGCTTTGTTCTACTGGCCCTGTTAAAACTCAAGCCAGATCACGTC 76_Target3.1_1 CACCTGCTCACAGCCCTCCTGTGGCTCCTCCTCACTCTCAGCAGAAA CTGACCTTCCCCCTCTTATCTCACCT 132 632327_266823 TCTGCTGTCTCCAGGTGGCGGCGAGGGAAAGCGCATCCTGGGGGAA 76_Target3.1_2 CCCTGGGCGCTTCCTCGCGTTAGACTCCCCCAGGTTGCCAACTGGC CAGTGGCTGGTTTCGGTACCCAGGCGTG 133 632327_266823 CAGAGTCACGCCCAGCGCTGCGCAGGCTGATCGCCGCGCCGCGCC 76_Target3.1_3 CCCGCCCTCGGTCGCAGGTGGCTCGTTCCGGGAATTCCTAAGCGGA AACCGGTCCCAAGCCCCGCGCCTTCGCTC 134 632327_266823 ATTCCACTTCGGAAGTTTTCGCCACCTCCCCCACCCGTTCCCAACTT 76_Target3.1_4 GTGGTTCGGCCCCTGGGCATCCCTAGCCCCCGGGTCAGCCCTCCGG AAATTCTGGCTCTTAAAGGGGCCGAGC 135 632327_266823 TTCGGGCCTCCTGTGTCTCCCAGTTAGATGACCTGAGGAACCCTCTA 76_Target3.1_5 AAGTCCCCGGAAGGGAAGCTCTGCCCCCTCAGGGATGCCCAAGGGG AATCAGGGCCAGGAAAAGTTGGAATTC 136 632327_266823 CGAAGCGCCCCCCCTCCACCCGGTCCGGAGGAACCCCAGTGGAAGT 76_Target3.1_6 GGAGAAGTCAGGCGCCACCAACAAGCCTCTCCCAGCCAGGACTTTG CTTAGACTCGCTCCTCCCGGCAGGGCGC 137 632327_266823 TGCAACCGAGACCCACTTGGAGCGATTCACCTGTTGAGATAGGGCG 76_Target3.1_7 GGTCCCGCCGCGCACCTGTTCCCTCCCTGCCCAAACCCCTCTCCCC GGCTGGCGATGGACCCGCCTAGGTGCGC 138 632327_266823 GCGCTCCGTCCCCCAGGGCCCGAACCAAGTGACTGGCCCGCTGGG 76_Target3.1_8 AGGGCGCCTGCGGACCACAGGTCCCTTCCGGCCCCCATCTGCTCCG GCCAAACCAAGCGCACCGAGATCCATGCA 139 632327_266823 CTCCGGTGAATGGTTCGGCCCAGGTACACAAGGGTGGGAGCCGAGG 76_Target3.1_9 GCTGGGCTTAGGGGTGAGCGGCGGGGAGGGGTTCCTCTGCCTCCC TCCCCGGAAGTGGGCTGACCCAGGTGCGC 140 632327_266823 GGAGCGCGCAGCGGGTGGAGTGTGGCTCGGAGGACCGCGGCGGG 76_Target3.1_10 TCAAGCACCTTTCTCCCCCATATCTGAAAGCATGCCCTTTGTCCACGT CGTTTACGCTCATTAAAACTTCCAGAAT 141 632327_266823 GCGCGTCCCTTCCAAAGTACCTTAGGGGGCGCGGCGCGCACCAAGG 76_Target3.1_11 CCAGGAGGGGTGCACGCTCCTCCCCTTCCCACTTCCGTTCCTTGTCC CTACTCCAAGTCCGTCCTGTTGCATTC 142 632327_266823 GCGCGGGCCAGACGCGCCCAGACGGCCGCGATGGCGCTGTTGGCC 76_Target3.1_12 GGCGGGCTCTCCAGAGGGCTGGGCTCCCACCCGGCCGCCGCAGGC CGGGACGCGGTCGTCTTCGTGTGGCTTCTG 143 632327_266823 ACCCCCGCTTCCCGCTTCCCGCCGCCTCCAACTCCATCCATCCCCCT 76_Target3.1_13 CTACAGTTCCCTCCGGCGTTCCGCAGCGTCAGAGGCCCCGTGCCCC GTACCTGTGCACCAGGTGCTAAGCAGA 144 632327_266823 TATCTTCCAGATAAGGGCGCGGGGAGCGCTCCCCGGCACAAATGGG 76_Target3.1_14 GAATTCCTCTCACTCCCGCGCGCAACAGATCGCCCAAGACCCAGGG GATCGGAAGGTCCCAGCCTCTGAGACCC 145 632327_266823 TCCCATCCCGGCTTTTCTTTTCCCAGAGATCGGGCGGTCTTCCACTC 76_Target3.1_15 CCTCCCCACAAAGAGTTCCATTCTCCCTGCCGCTCCGGGTCTCACCG TCCAGGGAGTTTCACTTCCTGCTATC 146 632327_266823 ACCCGAGGCCTAGGCATTGTTCCTTCGTCTCTGTCCCTCTAGGAAGC 76_Target3.1_16 GTCTGATCCAGCCCTCCCGTGCCCTCTCCCCGTTACTCCAAAACTTA GAAATCCCCGGGTGCGCCCAAGTCCC 147 632327_266823 CAGAAGTCGGTTTCAAGTCCGTAAATCCATCCCACCAGACTCTTACG 76_Target3.1_17 CACGTATAATCCGGAGCCCGCGGGAGGTGGGTGGGGTGCGGGGGA TGGGGAGTCCCCAGTCCCACACCCACCC 148 632327_266823 TCTGCTGGCAGGCTTTCACCTGGATGGGATATTTGGGTGGTGATGAG 76_Target3.1_18 GTCTTTCCCGAGACACTTTTGGTTCAGTCATTTGAAATGACTTTAGAG TAGGGTGAGGTGGTGGGAGGCTGAT 149 632327_266823 ACCGACTACGAAGGATTCCAGGTTACCCGGGGCCTTTTGAATTTGGA 76_Target3.1_19 GGGAAAACCATGGAGTTGTTTGCCTGAACTGCTTTGCCATGGAGGGA CTAAAGCCCCCACAATATCTCCATCA 150 632327_266823 CACCAGTCCCCTCTTCCCTTTGCCATTCACCCACAACAAGGGGCCTC 76_Target3.1_20 TGTGTGGCCTGGGCAGGCAAGCCCAGATGGCCATGTTGATGCCCCC AGCGCCCAAGGCCCCACTTCAAAACCG 151 632327_266823 GGTGTGGTTCAGAGGCCACAGGCTGGGAAGAGGGATGGCGGGCGA 76_Target3.1_21 GTCCAAGGAAACTGGCCGTGTCACCGTGCACCTGCCACTTCAGCCC CACGGGTCTATAAAATGGGCATGATTAT 152 632327_266823 GTGCCAGGCACTCTGTAAACCACATACTTGCGAGTGTCAAGCTGGTG 77_Target3.2_1 ACAGGTGGCGTTCCTGTTGAAGCACCTCCCTGAGCTCACAGCAACCC TTGCTGTCTCTCCTCTTGCCCTCAGC 153 632327_266823 TCTCTCCTCTTGCCCTCAGCTCCTGCCAGGGCCATCCAGGTGACCGT 77_Target3.2_2 GTCCAACCCCTACCACGTGGTGATCCTCTTCCAGCCTGTGACCCTGC CCTGTACCTACCAGATGACCTCGACC 154 632327_266823 CCTACCAGATGACCTCGACCCCCACGCAACCCATCGTCATCTGGAAG 77_Target3.2_3 TACAAGTCTTTCTGCCGGGACCGCATCGCCGATGCCTTCTCCCCGGC CAGCGTCGACAACCAGCTCAATGCCC 155 632327_266823 CGACAACCAGCTCAATGCCCAGCTGGCAGCCGGGAACCCAGGCTAC 77_Target3.2_4 AACCCCTACGTTGAGTGCCAGGACAGCGTGCGCACCGTCAGGGTCG TGGCCACCAAGCAGGGCAACGCTGTGAC 156 632327_266823 GCCAGTCCCACCACCCGGGCAAGCCCAGCCTCATCCCCCTGCCCTG 77_Target3.2_5 CCCAACATACTTCCGGTGATGGTAATCCTCCGGCCCTGGTAGTAATC TCCCAGGGTCACAGCGTTGCCCTGCTT 157 632327_266823 GCCCGGGTGGTGGGACTGGCGTCCTTGTGCGGGACCTGGAGTCCC 77_Target3.2_6 CATCTGAAAGCTCTTGAGTGCCAGTGTCTGAAAGGACCATTGAAGGG AGCAATTCTTTTTTTTTTTTTTTTTGA 158 632327_266823 GTGTGCAGTTCCTGGCATGTCACAGGCTTTCTCCATTAAGCTCTCTTG 78_Target3.3_1 CCCCTGCAGTTCACTCCTGCCATCTCCTCTGTGAGTCCTCTGCGGAC CACCCTAGGCAAGCAAAGGGATTAG 159 632327_266823 GTAACCTCTCTGTGCCTCAGCTGTCAGGAGGGTAGAGGAGAGGACT 78_Target3.3_2 CAATGGGAGAATATGTGTGCAGTTCCTGGCATGTCACAGGCTTTCTC CATTAAGCTCTCTTGCCCCTGCAGTTC 160 632327_266823 CCTCCCAAAGTGCTGGGATTTGTTTCCGGTTTTTTTCCTACTATGCTA 79_Target6.1_1 TAGTTTTGACTTTGTTTCCCTGACTAGGATGTCAATTCCGTGAGGCTG GATTTTTGCTGATTTTTTTTTTTA 161 632327_266823 ACTATGCTATACTTTTGACTTTGTTTCCCTGACTAGGATGTCAATTCC 79_Target6.1_2 GTGAGGCTGGATTTTTGCTGATTTTTTTTTTTAACCTCTGTACCCCTAG CTTTTTTTTTTTTTTTTTTTTTT 162 632327_266823 GCTTCCTCCGCGGCGCTTTAACACGCAGGGCGCTGCTGCCAGGGGC 80_Target6.2_1 GTCCCGTGTTCTAACTCGCTCCCACAGCCCCTCCGGCTTGGTGAGCA GCGTCTGAGGGGTGAGGGGCATAGACT 163 632327_266823 GGGGGCTCTGTGGATGGCATTCGGGGAGCTACAGGTTTCCCCCAAA 80_Target6.2_2 AGCTCAGATGCTCGTTCTTGAAGAGGGAGGTGCTGCCCCTGCCTTCC TGCGTACCGCGACAATACAGCTTCCTC 164 632327_266823 GAGCCCCCCTCAGTCGGCCTCCCCTGAGGCACCAAGGCTGGCGGAA 80_Target6.2_3 GCAGTCACCTGTCCATCTCCCCCACTTCTCACAGAGGAAATCCTGGG TGGTGCCGGGCAATGAGTCAGGGCTGA 165 632327_266823 CCTAAGGCCAAGGGCGCCTGGGCCCTGCAGAGGAGCGGAGCAGGG 80_Target6.2_4 GGAGGAGCGCTGAGACCTGCCCGTTGGAGGAATGCTGAGACGCCC CACCCAACCTCTGTCCTGGTCCTCAGCCCT 166 632327_266823 TTGGTGCAGGCAGCTTCTGGGCTTGAGTCCGGCCCCCTGCACCTCC 80_Target6.2_5 AGTCCACACTCCCCAGGAGCTCACCTGCTCCCAGGTCGAACTCCATG GCGGTAAGAGAAGTTGGGTCCTAAGGC 167 632327_266823 TCCGACCGGCCCTGAACTTTGTGGGGACTGAGCTTGGGATCTCCCC 80_Target6.2_6 CGTGGCCCGCCCCCACACCGGGCTTCTGGGAGGTGGGCTCCAGGG CTGTGGAGAGAAGTTGGGTGGTTGGTGCA 168 632327_266823 TGAAGTTGGAGGCCTAAGGCAGGACCCTGGGGTCAGGGGCAACCCC 80_Target6.2_7 AGCCTTCCCGCCCCTCCGCAGCCGGTGATGAGGCGACTTACCTTTG GACCCGGACCTGCCCCTGCCTCCGACCG 169 632327_266823 TACCTTCACATCCGTGTCCGAATCGCTGGAGCTGCTGCTGGAGTCGG 80_Target6.2_8 AAGAGCTGTGGTGTCCTTGCTGGATGGAGGTGCGGCAGTGAGGCGG CGCCCCTTACCCAGCCCCCTGAAGTTG 170 632327_266823 GGCTGGAAGCGAGACAGGGGGACCACTCCCCGCACCCTCCCCGCC 80_Target6.2_9 AGCCCCAGTGCGGGGACGCCTCTCTGGGGTGCAGGGCACGTGCTT GGGGACGCTGGCGAGAGCCCCTTACCTTCA 171 632327_266823 TTCCAGCCCAGAACCATCTCTTCTCTCCCATCCCTGCCCTCGGCCCC 80_Target6.2_10 ACAGTCCCACGCTGCTGGCTCCAAGCAGCACGAGAGCATCCCGGGC AAGGCCAAGAAGCCCAAAGTGAAGAAG 172 632327_266823 AGAAGGGCAAGAAGAAGGAGGCTCCCCACTGAAGGGCCCTGGACAG 81_Target6.3_1 GGCTCATTAAACCTTCCTCTCTGCCTTCTGCGACTGGTCAGCGTGGT GCCTACTCTGGCCCGTCCCCAGCTCCC 173 632327_266823 CCAGCTCCCTGCCCCCTGCCCAGCGCTGGGCCCGCCCATTCGTGCG 81_Target6.3_2 CGAGGCCAAGGAGAGGCTGTCCACGCCATGCCCATCAGGGTTTATT GTTTCTGTAACAGCGGCCACGCCCTGGG 174 632327_266823 GGCCCCAAGGTCCACCCTGTCTGGCCACAGGCACCGCCTCCATCCC 81_Target6.3_3 ATGTCCCGCCCAGCCCCGCCCCCAACCCAAGGTGCTGAGAGATCTC CAGCTGCACAGGCCACCGCCCCAGGGCG 175 632327_266823 CATGTACTGGCTCACCTTCCACCTGGTGCGGTGAGCGCGCCCGCTG 81_Target6.3_4 AACCTCCCGCTGCTGCTGCTGCTGCTGGGGGCCACTGTGGCCGCCG AACTCATCTCCTGCCTGCAGGCCCCAAG 176 632327_266823 CAGTACATGAGCATAGGCTGCGCCGCCGCCACCGCCATGGTCAGGT 81_Target6.3_5 ACATGCGCAGCTGGTTCCGGGCCCCACGCACCGGGACCCCCTCAGC TGCTGCGTCTGCCAAGATCTTCAGCCGC 177 632327_266823 TTCAGCCGCAGCGTCCGGATCTGGGTGGGAAAGAGAGAGAGGAACC 81_Target6.3_6 AAGGGATTTACCCTTGAGCCCTCTGGGCCAGAGTGAGAGCCCGGAC ATACTTCCAGCCTCTGCCTAGAAGCCCC 178 632327_266823 AGGGCCCGGGGAGAAGCAAATCCTCACCATGTTAGGAGGTTTGGGG 81_Target6.3_7 AAACTGAGGCCCCGGGAGCAGAAACCTGAGGCTGCAGAGGGCCAG GGACTTGTCCCCAGCTGCCTGGGGCTTCT 179 632327_266823 GGGCCACGTCTCCCACCCCCTCAGGCCGGGTGTCCACCGGGAAGTC 81_Target6.3_8 CCCCTTCACCCGCTCCAAGACCTTGCCTGGCATTTGAGTATGGAACC TTCTCAGATTTTGCCCACAGGGCCCGG 180 632327_266823 ACGTGGCCCAGGATGCTGCCCCCCCTTATGCTGGCCACACGGCAAT 81_Target6.3_9 TTCTGAAGACACGCCAGAAATGCTATCTTTATTTTTATTAAAGGACAG GGTCTCTGGCCTGGTGCGTTGGCTCA 181 632327_266823 TGTGAGTCACGTGCTTGGCCTAAACTTTTAAATGATGAGACTTAAGTC 82_Target6.4_1 AAAGTTTATCCAAGGCTCTGCCCTGGCCCACCAGCCACCACAGTCTG CCCTCTGCTTCTCACATGC 182 632327_266823 CAGAATTTCCCTGGAAGGAGATTCTCTAGAGCCCTTCCCACTGGAGT 83_Target6.5_1 CAGGGGTGCTGGTGAAGAGCACTGGGGTCTGCAGGCTGGGTGGAC CCCAAGCTTAGTTGGATCCTGGGCAAAT 183 632327_266823 CCAGGCTGCTAGAGGCTGGGGATCCCCAGCACACAGGCTCCAGGCT 83_Target6.5_2 GGGCTCTCACTCTCATTCCACTCTCCTTACATGGGAGCCTTCCTGCC AGAATTTCCCTGGAAGGAGATTCTCTA 184 632327_266823 CTCCTCTCCCCACAGGCCTGTGTGGCCCAGCCATGCGCTCTCCCAC 84_Target8.1_1 TTGGGTCCCTGCCCTGGCCGCGGCCTGGGCTACCCACCCAGGTAGC CAAAGGAATCTTTTTTTGTTTTGTTTTG 185 632327_266823 GTGTTAGTTATTACTCTCAACATCTCTTCAAACCACCTTTATGCTTGCC 84_Target8.1_2 TCTCTCAGACTCCTCTTCCTCCTCTCCCCACAGGCCTGTGTGGCCCA GCCATGCGCTCTCCCACTTGGGTC 186 632327_266823 GAGAGGCAAGCATAAAGGTGGTTTGAAGAGATGTTGAGAGTAATAAC 84_Target8.1_3 TAACACTTGTTATCTCATTCAATCTTCACAAGATGCAATGAAGAAGTG GGCTTTTTTTTTTTTTGAGACAGAG 187 632327_266823 AAATTCACCTATTATTCCAGCTTCTCTCTTCCAAATACGGCCTCTGTG 85_Target8.2_1 CCCTGTTTCTTCCCCCAGGAGGAGATGAACGGCTGGCTGGAGGCTG TAGCTTCCTCGGTGGCGGAACACGCA 188 632327_266823 GGGGTGGGAAGTCACTTCCTGCGCCCGCTGGCCCTGCGATCTCCGC 85_Target8.2_2 CTTCCCTCTTAGGGTTGCCCTCATCTGTGGATGAAGTAGTGGGTAGT GTCTGGCCCCAGCGGGCGATCTCTGCG 189 632327_266823 CCCACCATGTCACGCGTCCTCAGTGTTGGAACTAGGGGCTCCCGCC 85_Target8.2_3 CCTGCGGAAGAAAAAGTGTCTTTGTGCCCACAGTGCGGAAAAGAGG GGAGACGAGATGTGTCAGGTCCTGGGGG 190 632327_266823 GACCCCCAGCACCTGGGGTGGGGGTGGTGAGTGGGAAGGGGCCGA 85_Target8.2_4 GATATGGCTATAGGGGCAGCAATCTCCCCACCACTTCTTGGGGTGCA GGAGAAGTCCCCTCCTTTCCGGTGCCCA 191 632327_266823 TACTGCCCCCACCACCCCAGCTTCTTGGGGCAGGATCTGCAGATCG 85_Target8.2_5 GGGCTGGGGGCTTGGCTCAACTGGCCCCCTGCCCACCCCCATCAAG CTCAGTTATTGCATAAAAATAAGGGACC 192 632327_266823 GTGAGGTAAAGGCGGGGAGGGGGTGTCCCCTCCCTGCCCCCTAGC 85_Target8.2_6 ACCCTGGATGGTCCAGGGGACCTCACCAGCGCCCCCGTGCCCATCC CTAGGGCAGAGAGGGGGGCAGGAATTACT 193 632327_266823 TTTTGCAAAAATAAACTAAGTCAGGAATTAACCGCATGGCTCTGAGGC 85_Target8.2_7 GGCGGAGTGCAGGGGGCTAGGGCCCCTTCACTCCCCCCTCCCAGA CAGAGATCAAGGCAGCATTGGAAGTGA 194 632327_266823 CATGAAGTGGCATTTACAACTGGAGGGGGGAGGAGAGAGGAAAACA 85_Target8.2_8 GTTTTGAGCTTTGACGCCCCTCCCATTAAAAGCCTTCGCGGATGCGG GGCGGGGGAGGAGGAGATCGACGTTTT 195 632327_266823 CCCCAGCGGCTTCTCCAGGCGGCCATGGGGACTGCCCACAACCCAA 85_Target8.2_9 TCCCCCGACTCCCCAGGGAGGTGCTCCAGCCAGAAGCATGCAGGGG TGGGCTTCCCCTCGCCCCTCCCCTCATG 196 632327_266823 AATCCTCCCGGGCGCAGCCCAGAAAACCCAAACAAAGGACCATAGA 85_Target8.2_10 CCGTCAAAGCCAAAGGGTTTATTATAGGTACATACAGTGTGCGCCCG CCACACCGCCCCACACCCCCGGGCCCC 197 632327_266823 CCCCGAAATTAAGTCCACATAAAAGGGTACATCTGGATGTTCTCCGC 85_Target8.2_11 AGCCACGGTACCCCCGTGCCCCTCTCCCCACCCCGCACCCACCCCT ACAGCCACCACAGCCCTCCTTTCAATC 198 632327_266823 CGCCTTTCCTGAACTTGACGGGGCGGACCCGGAGTCTCCTTTGGGG 85_Target8.2_12 AAGTTTATTACGAAGCATAACGAAATATTCTCCATCCCTCTAGGTTCT CGTCAAGGGGCGTGTGTTTAGACCCC 199 632327_266823 GCACCCGGACCCCGCCTCCATAGGCTGCTCATTGGGCCAGAGACTC 85_Target8.2_13 CAGGAGTCACTAGCGATTGGACAGAGCGCCTGCCCATCGCGGTTAA CTTTTCCGCCTCCTTAAAGGGGTCCGCC 200 632327_266823 CATTCAGATGAATGACTTCCCCGGGAGGCCCCCGACTGGGGACCCC 85_Target8.2_14 CTCGGCTGCAGTAGCCGCTGCTGCCATGGCCCCCGGGCGAGCCGG CTGGCCCGCACCCACTTCCGGGTGTGCAC 201 632327_266823 GCGGAGCAACCCTTGATGGACAGGGATTCCCCCAGGAGAGGCGGAT 85_Target8.2_15 ACTCCCACCCCGCTTCCCGCCCCCGAGGATGGGACCTCAGGAGTCT CCCACACTCACCTCTTGCCTCCCACATT 202 632327_266823 AGAGATGAAGAGGAGCGGGTGAGGAATGCGTCCCCCTCCCGCAGGA 85_Target8.2_16 TCCAGGGTTCCCTCCCCTTCCCCCTCCCCCGGCGTTTTTCCAGAATC TCGCGCCTCCAAAGGGGGGGGGGGCGG 203 632327_266823 CTCCTACCCTCGCCCCAAACTCGCTCTCCCGATCACCTGGAGAAGAA 85_Target8.2_17 GGAGTCTGGGATCCAGGTGAGAGTCTGGCGAGAGGTACTGAATCTG GGCGGGGAAGGTAAACGGACGCAAGAG 204 632327_266823 GGAGGGATGGAGAGGGCGTGGGAGACCTAATATCCACTCCCCCGGC 85_Target8.2_18 CCGTGACGCCTGCTCGGTGTCCCTTCCCTGCAGTCTTCTGAGCGGA CGCATCTCGACGCTGAAAGATGAGACCG 205 632327_266823 GGGAAAGGGGGGCAGAGGATGGATGGGGTAAAAGGCAGGACTGAG 85_Target8.2_19 TGGGGTCCTGCCCCTCTTCCTACCAACCCCTCCCCCCCATCCCATTT CAGTTCTTGTCCGACTCACTGCTCCGGT 206 632327_266823 AGACAGTGAGGGACTCCCTCCCCTTTTTCCATGCCAACCTGGGATCC 85_Target8.2_20 AACTCTTTGGTGCGCAGGAAGTTGAGGATGGGGGCGAAGACTGTAG GGTCCCTGTCGATGAAGATCTGCGGGA 207 632327_266823 GTCTTCAGTCCCTGAGGAGTTCTTTCACCTCCTCTGAATGTCCACGT 85_Target8.2_21 GAGCTCCATTCTATTAGAATTCTCATTCAGAACCTTGATCACAGGCCG GGCGCGCCGGGATTGCT 208 632327_266823 ACACACACACACACACACACTCAACATTTCCTCCACCCATATCATCAC 86_Target8.3_1 TCCTTAGCATCTTTATTCCATCAAAACTTTCTACCCCTTGACATTCTCT GTGCAGTTTTGAAAATTACCCTC 209 632327_266823 GAGTGAGCCCATAGAACTGGGCTTCATGGAGGAGGCTGGAACCGTG 86_Target8.3_2 GACACCCCTGGGTAGTAGAATTGACTAGAGGTCAGGGTCTAGGTGT GGGGGTGAACAGAGAATGCTGAGAGGGT 210 632327_266823 CCACCTCTACCCCAGCCCTCTTTCAGGAGAGAAGGGGAAGAGGGGC 86_Target8.3_3 AGGTAGCATCACAGAGTTGGTTTTCTATACAATGAGGATGATAGCTG GGGGCTCCCACTTACCCAGAGGAGTGA 211 632327_266823 ACTTAGGGAGATGCTGAGGCCACCCCATTTCCCCCTCCCCATTTCTT 86_Target8.3_4 TCTACACAGAGTACCAATACTCCTCCCAGTACGAATACAGACCCGGC CAGGGCCATAACCAGTCCTCCCACCT 212 632327_266823 CTAAGTCCCAGCCTTTAAGTCCTCCTGTTGCAGTTCGTCGCCTGCAG 86_Target8.3_5 CTTCGAGAGGAGTTGGATCGATCTTCTTGTGGAAACGTCCTCTTCAAT GGTTACCTGCCGCCACCAGGTAGGC 213 632327_266823 GAACTACACCTCCCACTGTATCTCAGGACGCACAGCACAGGCACCC 86_Target8.3_6 GAGAGCTGCAGCCTTATGGGAAATGTAGTCTTTGGCCCACCTCCGCG CCCCTCCATTCCATTGGGAGTGCCTAC 214 632327_266823 TAGTTCCCTATCAGATGCTTGGGCTGATGCTTGGAAAGGAAGTTGGA 86_Target8.3_7 CACAGCATTTCCCATGAGACAATGGGCCAGCTAACTCTTGAGGCTCA GAAGGATGTCCTGGAGCCCCATGGGA 215 632327_266823 GGCTATCATGGGCATTACTGTCAATAACTTCCTATTAATATTTCTCCC 86_Target8.3_8 CTCCATACGAAGAATCCCAGGTCTTCCAAAGCCCCCCCTACAAAGAA ACCAAACCCGGACTACAACTCCCAT 216 632327_266823 ATAGCCAGCCCACTGGCCATGGAAGGTATGCCCCAGTGGTTATTGGA 86_Target8.3_9 ACTAGGCTTTTCTGATTGGTAGAAGTAACAGAGTAGGGAAATTTCATC TACAGCTTTATTTCCCTAACTGCAG 217 632327_266823 CTGCAGTCAGCACCTGCTACCTTCATGAAAGTTGCCAGATATAAAGAT 86_Target8.3_1 CTGTAGTAGTACTTTTCCAACTTAGTTTTATCCTGTTTTCCGAAAAACA 0 ATCATTTATTTATTTATTTATTT 218 632327_266823 CATTATATACAACCCAAGGCTTGCCACAAACTGAAATTTCTTATGCAT 87_Target5.1_1 TGACATTCAGCATTTGATGTAAAATGACAATCTTAGAGTCGCTGCCAC AAACCCTGGTAAAACTGCCCCTGC 219 632327_266823 CTTCTCCAGTTCACTAAGTTCAGCTACTCCTTCAGGGCTTGTGCTCCT 87_Target5.1_2 TTAAAACTTTTCAGAAGCCCCTTGAAGTACCAACATGTTGAAACTCAA ACTCAACTGCCTGCAGCTTCAGAT 220 632327_266823 CAGCTCTGGCCACTGAGAATTCTTCTCCAGGCCCCAGTGTCAAAGGC 87_Target5.1_3 ACTTTTGACCATCATGTGTTTGTCTGACTACCAAGTTGGACTGCCAAC CTTCACTAAAAACTCCGGCACCTTT 221 632327_266823 ATCTACCTCCTGTCAGATCACCGCCTGTCAGAGAGGGAGGCCTAAAA 87_Target5.1_4 AGGCTTCAGGATATCAACAGCTTTGAGCTGCCTTAGAGGAACTTCTTT TCTATTTTGTAGTACAGGAGCCTCA 222 632327_266823 TGCACTGCATCATCCAAACAAGACTCTCCACAAAACATTACTAATGGA 87_Target5.1_5 TTCTAATTGAACAGAGTTTGGTTACAAGAGACAGTAAACACAAATGGG CACCTGTTTTAAATGGCAAACTTA 223 632327_266823 CACAATAAATTCAATTGATCTTAAAAACTAAACATTCCTCTAAGGTTAC 87_Target5.1_6 TGACTATAAATATCTAGAAATTACTACTCCTATAGTCTTGCTATTTCCA GACAAGTGAAACTGGAAGGGAG 224 632327_266823 AGAGGAGAAATACCCAGTTATAATGACAAGACAACCTTATCTTTTCTC 87_Target5.1_7 AAAAGCCTCCCCAAACACACAACCATTTTCCACAAAACAGTTACATCA AAAAAGATGTAGCAAGACCTAGAC 225 632327_266823 ATTAAGCATGCTAGAAAGTAGGGACAGTTTTACCAGTGTTTGTGGCA 87_Target5.1_8 GCAACTCTGAGATAGTCATTTTACATCAAATGCTAAATGTCAATGCAT AAGAAATTTCAGTTTGTGGTAAGCC 226 632327_266823 CTGGGTTATATATAATGGCAACAAGAGAAAACTATCACATAATCTGAA 87_Target5.1_9 TTACGTTCATTTTTCTGCATACACCATGCATGCTGGTACACTTTCAGTT AGCCTAAACTTCACCCAAAAGTA 227 632327_266823 GAGGTGGCTATGAAAACTCTACCTGCATGGTATAAATAGATACCTAAC 87_Target5.1_10 CCTACATGCATGGGTCACTTGTATCTACCTCCTAAATACCAAAAACTT AGAAGCCCAGATTTCTTTTCAGTC 228 632327_266823 AAAAACAAAACAAAACAAAAAATTACCCTTCCCCACAATTATAAGCATT 87_Target5.1_11 TTGGCATATTTCCTTCCTGTCTCTGTTGTTCCTATTTTGGCAGTATTTT TATTGTTATCGCAGGCAGCCT 229 632327_266823 GCCGCACACCTTATACCTCTCCCCTTTAAAACAGACATATTAAAGACT 88_Target5.2_1 TCTGTTTTCTGAATTTACTGTAAACAGAATACTTAAAAAAAAATTACCC AGACAGGCGTGGTGGCTCACTGT 230 632327_266823 TGAACAAACTGCATTAGACTAAAATCTTTCACGAGTCCAAATTCTGCG 88_Target5.2_2 ACTAGAAAAATAAACTTGTTAGCCGCACACCTTATACCTCTCCCCTTT AAAACAGACATATTAAAGACTTCT 231 632327_266823 ACTTACTTTCTTGTTCTGACTCAACTCGGAAAACACCTCCCTAGTCTG 88_Target5.2_3 AGGCCCCCCTCCTTATATTTGTGAACAAACTGCATTAGACTAAAATCT TTCACGAGTCCAAATTCTGCGACT 232 632327_266823 TTTCCACTATATCACACTGCACTGTCTGGCTCCAATCTGATGGCGAG 89_Target5.3_1 CAATGGTTCCTTAAAAAGCTCCATCTTCTCAAGCCTACCCAGCACAGA CCTACAACTCAAACTTTAAGTTTTA 233 632327_266823 AGCCAGCCTAACCTTCCACGTCCACTTGAAAAAAGAAAAAAAAGAAA 89_Target5.3_2 GAAACAATCAACCGGAAGCCTTTGATTTTTTTGCTAGCAAGAAGCCAA TAATTGTTTTCTTTGGGACAATCAC 234 632327_266823 CAGGTTAAGTTGTGAAATGGGTGGCAGAAACTGCAAGATTTAACCAG 89_Target5.3_3 TTTCTCTCAACGCTAATCAAAGGTCAAGAAAATAAAAGACAGGGCAGT GAGAGTCGCGGGACTTTAGACACTC 235 632327_266823 AGTGTGGAAACCCCTTCCCCACTCAGTCCAATTTCAAGGTTATGGAG 89_Target5.3_4 CATAATTAAGAGTGACCATTCTAAAAGCGTTCTCTAGTGCCCTGGCTA AGACTTTTAAGCTTCTTGGTGCAGG 236 632327_266823 AGAAGCAAAGATGATGTCTGTCACCTGGCAGCGTAGACGGAGAGTG 89_Target5.3_5 GCGGTAGATGACTTGAATGGACACGTGGATTCGAGTCTGGGGACAG GCGTTCCCCCAGTCGGTGCGTTGTGAGA 237 632327_266823 TCAATTTCAAAAAATGCCAGCACTCCTTAGATCAATGACTCCACGGCC 89_Target5.3_6 AAGTGCAAGGGCCACGGGCACTCCTCTGGAGTCACCGAGAGAATGT CTGCCTCTGGCAGCGGCCTCTGAGCT 238 632327_266823 GGCCCCCGCCTGCCCAGAGGCCGGGCTCGCGGGCGTTCGGACCGC 89_Target5.3_7 GCGTGGGGCGAGACTGCACTCGCGCCCGCTGAGATGCCGGCCCCA CGCAGCGCGGCGGCACGAGGCCCACAGGCA 239 632327_266823 CGCGGACGAGGGCAACGTCAGCGGCCCAGCTGGGCCACCTCCTCC 89_Target5.3_8 CAGCCGAAGCGCGGCCTCCGGCTGCTTCGCCGGGCCGGTCCCCGC CGCCGCACACACAAGGGTCGGTCCCGCGCG 240 632327_266823 CTGCCCGCGGCCCCGCTTCCCTCGGCAGCCGGAGGCCTCCGGGGT 89_Target5.3_9 GCCCGTGCTGCCGCAGCTTCCTGTGTCTGAGTCGCGGGCGGCGCG GGCGCGGGGCTGGTGCGCGGCCGGGGATGC 241 632327_266823 GGGCCCCGGCCGAGGCGCCGGCTGACGTTGCCCTTCAGGGCCGAG 89_Target5.3_10 CCCGGAGCAGCGGCCGCCGCGGAGGCGCGTGAGCCACCCCAGGCT CGTGGGGCCGCGCCGCCTTTCCGGCCTCC 242 632327_266823 GCCGCGGGAGCAGGCGCGGCTCCGCACGGCGGGCGCACTCACCTC 90_Target5.4_1 CTCCGTGGACCGGCCGCTCCGCCGCCGGCTGTCACTGCAGCCCACT CCCTGCCCCGCGCCGGCTCTGGATGCTAT 243 632327_266823 TCTGGATGCTATTTAAGGCGCCGCTGGCGCCGCCGCCTCGGCCCGC 90_Target5.4_2 TGGTTGCGCCCCCGCCACCGCCGCGGCTGAGCCAGGATGCTGCTG GTGCGCTCGCCGCGCCGGCCCCGCCCTCC 244 632327_266823 CGCCGAGCGCCCGGCCGCCCTCCTGTCTGGGCGCGCGTGGCTGGC 91_Target5.5_1 GGGTGGCCGGCGGTCGAGAGGCTGCGGCGGGCGAACGCCGCTGG AGTCGCCCAGACTGCCTCGGATTTCATAATG 245 632327_266823 CAGGATCCGGAGGGCGCCGCCCGCCCCTCGGGCATCGCGGGGCCC 91_Target5.5_2 AGGGTCCGCGGGGCCTCTGAGCTGAGGCGGTCCAATGTACCCTTTG TCCTTCCTCAGATTCATTATGAAATCCGA 246 632327_266823 GCCCTCCGGATCCTGCACCCTCAGCCCGTGCCCCGCTGGCCTCCTG 91_Target5.5_3 GCAGGCCGGGCAGAATTCTGCTGCGAGGGCCCTGGAGGCAAGGGC CTTCCTCTCCGTTTTTCCTTGACACTGAC 247 632327_266823 TTCCTTGACACTGACGGGCGCGGCCCCACAGGGTTTCCCCCACGCT 91_Target5.5_4 CCCTGGCCGGAAGACCTTTTCTGTCTGGTGTCTGCAGAGCCTGACGT GGGCAGCGCCCGCAGCTCGCGCCGGTG 248 632327_266823 TGGGCATGGCAGGGACGCGGAAGCCCTCAGAACCGCGGAAGCCCT 91_Target5.5_5 CAGAACCGCACAGCAGGTGGCCGCCGTGGTGCAGCGCGCAGTCGG CCCTCAGCTCCCCTGCACCGGCGCGAGCTG 249 632327_266823 GTTGTTAGAGGTTGAGGTTCCTGGTAGGTCCCAGGTGCTAAAAGGAA 91_Target5.5_6 GAGCAGCCTTTGGGATGTGAGCCCGAAAACCATCGTGTTGGCTTCTG AAGCCCCAAGATGGGCATGGCAGGGA 250 632327_266823 TCAACCTCTAACAACATTGGTCCCCGTTACCGTGGAGTTTGCGCCCA 91_Target5.5_7 GCGTTCGCTGGAGGGCCGTTTGAAGAATGATTGTTGTCGTAAAGGCC TTTGATAATAATAGATACTGTTTACC 251 632327_266823 GTCAGTTTCCCCTGCCTGCAGCCCAGGCATAGCCCTGCGTTGGTTGT 92_Target5.6_1 GCCCACACTCTGGGGGCAGCCTGAGTGCCAAGTGTGGTACTGCTCT CACTAGCATTTAACCTCTGTGCCCCAG 252 632327_266823 TGCGCCCAGCACACTGTGGGAGACACCCAGGGAAAGTCCTTCAGTT 92_Target5.6_2 ATTTGTGGGAGTGAACTGCAGTGTGGCTGAGGCCTGGAGCGAACCA CGGTCAGTTTCCCCTGCCTGCAGCCCAG 253 632327_266823 CCATTTTTTCTAGATCTGGAAGATGGAGATCTAAAAGGACTGAGCTGC 92_Target5.6_3 TAGAGAGGTTGCTGGTGTGTGCGTTGTCCTCACCCCACTGCACCACT GCGCCCAGCACACTGTGGGAGACAC 254 632327_266823 CCATCTTCCAGATCTAGAAAAAATGGACTCCACGTTCGTTTTCACTGG 92_Target5.6_4 TTCCCGCTTGGCTAATCCCTGGTTTTTCTGTCCAGATCTCGCCTCCCC ATCCGTGATTTTGTCATCTTTGCC 255 632327_266823 CCATCCGTGATTTTGTCATCTTTGCCTCTCCTTTTTCCTCTTCTCCAAC 92_Target5.6_5 CGGTCCCTCAGCCCCAGAACCTCTGCAGGCACCTCCCAAGTTCTGT GGTCTATTGTTTTCAAGGGCTGCTG 256 632327_266823 TGACAATTCAACCCGTAACATGTGGATGGTCGTCACTGGCTGTCTCA 93_Target5.7_1 CCTTACGTCTTCTCCTCAAGACACTTTTCTTTTAAACTGGGTGCCTCT CCCTGGGCTCTAGCCCTTAATGAGG 257 632327_266823 AAGACACTTTTCTTTTAAACTGGGTGCCTCTCCCTGGGCTCTAGCCCT 93_Target5.7_2 TAATGAGGTGATTTCCAACTCAAGGCTGGGAAAGGCACACAACCCAG TATCAGACCTGAGTTCACACTCCTT 258 632327_266823 CCCATACATTGTAAAACTTTTTGGAGTGATTAGATAAAAACTTTTTTGT 94_Target5.8_1 TTTTTTTTAAGTGTGTGTGCTGAAAGAGACCTAAGAGATTATTTAGCC AAGCCCCCTTATAGCCTGAGGAG 259 632327_266823 TCTTAACCACTATGCAATACTGCCTCCCATCAAAGTCTCTATCTCAAG 94_Target5.8_2 TCCACAAGACAACCCCATACATTGTAAAACTTTTTGGAGTGATTAGAT AAAAACTTTTTTGTTTTTTTTTAA 260 632327_266823 GACAGGTGTCATAGGATTGACAGCCACGCCCTTGGCGTTCTCATTAA 95_Target5.9_1 ATGAAGATTCCAGACTCTATAGTTGGGAGTTTGTGACTTAGGTAAGAA ACCAGTCTCTTTTTTTGAGACGGAG 261 632327_266823 TGTCATAGGATTGACAGCCACGCCCTTGGCGTTCTCATTAAATGAAG 95_Target5.9_2 ATTCCAGACTCTATAGTTGGGAGTTTGTGACTTAGGTAAGAAACCAGT CTCTTTTTTTGAGACGGAGTCTCAC 262 patch CTCTGTCGCCCAGGCTGGAGTGCAGTGGCACAATCTCTGCTCACTG CAAGCTCCGCCTCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCC GAGTAGCTGGGACTACAGGCGCCCGCT 263 patch GCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCAC CGCGCCCGGCCCACAGCTCTAGTTCTTTAATACACATCAGGTCGGTC ATGGTGGCTCATGCCTGTGATCCCAGC 264 patch TTGCTATGTTGCCCTGGCTGGTCTTGAACTGCCAGCCTTCAGGGACG CTCCTGCCTTGACCTCCCCAAATGCTGGGATCACAGGCATGAGCCAC CATGACCGACCTGATGTGTATTAAAG 265 patch GAGCGTCCCTGAAGGCTGGCAGTTCAAGACCAGCCAGGGCAACATA GCAAGACCCCATTTCTACAAAAAATTAAACAGCCAACCAAAAAAAAAA AAAAAAAGAAAGAAAAACTTTAGCTG 266 patch CCTGGGCTCAAGCAATTCTCCTGCCTCAACCCCCCAAGTAGCTGGGA CCACAGGCATGCTCCACCATGTCCAGCTAAAGTTTTTCTTTCTTTTTTT TTTTTTTTTTGGTTGGCTGTTTAA 267 patch GACAGGGTCTGGCTGTGTCACCCAGGCTGGAGTGCAGTGGTGTAAT CATGGCTCACTGCAGCCTCGACCTCCTGGGCTCAAGCAATTCTCCTG CCTCAACCCCCCAAGTAGCTGGGACCA 268 patch CATGATTACACCACTGCACTCCAGCCTGGGTGACACAGCCAGACCCT GTCTCAAAAAATATATATGTATATTTTAAAATATTATATATTATATAATG TAAATAATATACATGCTACATAT 269 patch TTTTAAAATATTATATATTATATAATGTAAATAATATAGATGGTAGATAT TTTATGTATACATCTATGTTATATACATTAATATAGCCAGGTGCAGTGG CTCACACCTGTGTTCCCAGCA 270 patch ATATACATTAATATAGCCAGGTGCAGTGGCTCACACCTGTGTTCCCA GCACTTTGGCGGGATTACGGGCGGGTCACCTGAGGTCAGGAGTTCG AGACCAGCCTGGCCAATATAGTGAAAC 271 patch GGTCACCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAATATAGTG AAACCCCGTCTTTACTAAAAATACAAAAAAAAAAAAAAATTAGCCAGG CGTGGTGGTGGGCGTCTATAATCCCA 272 patch AAAAAAAAAAAAAAATTAGCCAGGCGTGGTGGTGGGCGTCTATAATC CCAGCTATACAGGAGGCTGAGGCAGGAGAATTGTTTGAACCCGGGA GGCGGAGATTGCAGTGAGCTGAGATCG 273 patch TTCCCCTTTGGATTTTTTTTTTTTTTTGAGACAGAGTCTCGCTCTGTCA CCAGGCTGGAGAGCAGTGGTGCGATCTCAGCTCACTGCAATCTCCG CCTCCCGGGTTCAAACAATTCTCCT 274 patch GTGCTGATGGTAATAACCTTGACCACGTGGTCAGGGCATCTGCCGGT TCCTGCACTGTCCAGTTACTGTTTTGGCCTTTGGATTTTTTTTTTTTTTT GAGACAGAGTCTCGCTCTGTCAC 275 patch GGGAGTCCCGGGCGTGGCGTGTGTCTGTCTCAGGCCCCCCACGTC GAAGCCCATGGCTTCGGCCTGTCTCGTGCTGATGGTAATAACCTTGA CCACGTGGTCAGGGCATCTGCCGGTTCC 276 patch ACTCAATGGAGGGAGTCCCGGGCGTGGCGTGTGTCTGTCTCAGGCC CCCCACGTCGAAGCCCATGGCTTCGGCCTGTCTCGTGCTGATGGTA ATAACCTTGACCACGTGGTCAGGGCATC 277 patch CCTCTAACCCTGGGGTGATTCTGCCCCCAGGGGTCCCTGTGTGAGG CCTGGAGACATCCGTGGTTGTCACGACTTGGAGGGAGCTCCTGGCA GGGCCCTGCAGTGCCCAGGATGGCCCCG 278 patch CTCAGAGTCTCTTGGGGTCTGTGGAATCCTCTAACCCTGGGGTGATT CTGCCCCCAGGGGTCCCTGTGTGAGGCCTGGAGACATCCGTGGTTG TCACGACTTGGAGGGAGCTCCTGGCAG 279 patch AGGGAGCCAAGATCGTGCCACTGCACTCCAGCCTGGGCAACAGAGC AAGACTCCATCTCAAAACATAAATAAATAAAAATAAAAAATAAAAAATC CAGTCTGCCCCCTGCTCACACCGGA 280 patch TCTTGCTCTGTTGCCCAGGCTGGAGTGCAGTGGCACGATCTTGGCTC CCTGCAACCTTCGCCTCCCAGGCTCAAGTGATTCTCCTGCCTCAGCC TCCTGAGTAGCTGGGACTACAGGCGC 281 patch ACCAGCCTGGCCAACATAGTGAAACCCCATCTCTACTAAAAATACAAA AATTAGCTGCGCGTGTTGGCGGGCGCCTGTAGTCCCAGCTACTCAG GAGGCTGAGGCAGGAGAATCACTTGA 282 patch GCCTCACACCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGG ATCGCCTGAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATAGTGAA ACCCCATCTCTACTAAAAATACAAAAA 283 patch CGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGTGTG AGGCACCGCACCTGGCCATTTTTTTCCCCAAATAATGAACACTGGTCT CTCCCCTGGGCCCTGTGGACATCGGG 284 patch GTGGAGGCCAAGGATGATGCCTAGCACCCTGCAGTGCCCAGGACGG GCCTGCCCCAGAGAAGGATCCAGCCCCGATGTCCACAGGGCCCAGG GGAGAGACCAGTGTTCATTATTTGGGGA 285 patch AGGCCCGTCCTGGGCACTGCAGGGTGCTAGGCATCATCCTTGGCCT CCACCCACTCCATGCCAGGAGCTCCCCTTTCGTGACAGCCACAGGT GTCCTCAGACCTCGCCCAGGGTCCCCTG 286 patch TGGGGGTTTTCTTCCCCCTTTAAGGCCAGGATTCTCAATCAAGAGGT GATTCTGCCCCCAGGGGACCCTGGGCGAGGTCTGAGGACACCTGTG GCTGTCACGAAAGGGGAGCTCCTGGCA 287 patch GAATTCGCCTGTTACTAGCTAATTCCCAAAACAGCTCCTCAGGAGGG AAGGGCTGGGTTTTGCCCGTTTTACAGATAGGCAACTGAGTCAAATG GCCAGGGCTCCCCCTTGCCCTTGTCC 288 patch CTTCCCTCCTGAGGAGCTGTTTTGGGAATTAGCTAGTAACAGGCGAA TTCCTGGACAGCACCCAGCCTTCAGCAAATGCTCAGTGAATATGCAT GAATGAATGAATGAGTGAATGAATGA 289 patch CCCCTCAGGTCCCTATCCTGAGGGTGATTTTCTTTTTCTTTTTCTTTTT TTTTTTTTTGAGACGGAGTCTCGCCCTGTCGCCCAGGCTGGAGTGCA GTGGCGCGATCTCGGCTCACTGCA 290 patch CGCCCTGTCGCCCAGGCTGGAGTGCAGTGGCGCGATCTCGGCTCAC TGCAAGCTCAGCCTCCCGGGTTCACGCCTTTCTCCTGCCTCAGCCTC CCGAGTAGCTGGGACTACAGGCGCCCA 291 patch AGACCATCCTGGCTAACACCTTGAAACCCCGTCTCTACAAAAATTACA AAAAATTATCCAGGCATGGTGGTGGGCGCCTGTAGTCCCAGCTACTC GGGAGGCTGAGGCAGGAGAAAGGCG 292 patch CGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGCAG GCGGATCACGAAGTCAGGAGATCGAGACCATCCTGGCTAACACCTT GAAACCCCGTCTCTACAAAAATTACAAA 293 patch CCGCCTGCCTCAGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCC ACCGCGCCTGGCCCTTTTTTTTTCTTTTTTGAAACGGAATCTTGCTCT GTCGCCCAGGCTGGAGTGCAGTGGTG 294 patch GCTACTCAAGAGGCGGAGGCAGGAGAATCATTTGACCCCAGGAGGC TGAGGCTGCAGTAAACTGAGATTGCACCACTGCACTCCAGCCTGGG CGACAGAGCAAGATTCCGTTTCAAAAAA 295 patch GTGGTGAAACCCCATCTCTACTAAAAATACAAAAACTAGCCAGGTGT GGTGGTGTGTGCTTGTAATCCCAGCTACTCAAGAGGCGGAGGCAGG AGAATCATTTGACCCCAGGAGGCTGAG 296 patch TTTGCAGATGAACAAACTGAGGCATTGAAAATCCCCCTCAGGTCAGG AGTTCGAGACCAGCCTGACCAACGTGGTGAAACCCCATCTCTACTAA AAATACAAAAACTAGCCAGGTGTGGT 297 patch AACAAAACAAAACAAAATAAAAAAAAAGAAGCAAAAAAAAAAAAAAAA ATCAGCCAACAAAGAGACCCATTTTGCAGATGAACAAACTGAGGCAT TGAAAATCCCCCTCAGGTCAGGAGT 298 patch AAAAAAAAAAAAAAAAAAAAAAAATCCTGGGCGCAGTGGCTCATGCCT GAGTGAGACCCCATCTCAAAAAAACAAAACAAAACAAAATAAAAAAAA AGAAGCAAAAAAAAAAAAAAAAAT 299 patch TCAGGCATGAGCCACTGCGCCCAGGATTTTTTTTTTTTTTTTTTTTTTT TGAGACAGAATCTCACTCTGTTGCCCAGGCTGGAGTGCAGTGGTGTG ATCTCGGCTCACTGCAACCTGTGC 300 patch TGCCCAGGCTGGAGTGCAGTGGTGTGATCTCGGCTCACTGCAACCT GTGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCAGGCA GCTGAGATTACAGGTGCGAACCACCACA 301 patch TCCTGCCTCAGCCTCCCAGGCAGCTGAGATTACAGGTGCGAACCAC CACACCTGGCTAATTTTTTTTTTTTTTTTTTTTGAGACGGAGTGTCATT CTGTTGCCAGGCTGGAGTGCAGTGG 302 patch TACTCCGGAGGTTGACGCAGGAGAATCGCTTGAACCCAGGAAGCGG AGGTTGTGGTGAGCCAAGATCGCCCCACTGCACTCCAGCCTGGCAA CAGAATGACACTCCGTCTCAAAAAAAAA 303 patch ACCTCCGCTTCCTGGGTTCAAGCGATTCTCCTGCGTCAACCTCCGGA GTAGCTGGGACTACAGGCACGTGCCACCACGCCCAGCTAATGTTTGT ATTTTTAGTAGAGACAGGGTTTCACC 304 patch CCACCACGCCCAGCTAATGTTTGTATTTTTAGTAGAGACAGGGTTTCA CCATGTTGGCCAGGATGGTCTCCATCTCTTGACCTCAGGTGATCCAC CCACCTCGGCCTCCCAAAGTATTGG 305 patch CATCTCTTGACCTCAGGTGATCCACCCACCTCGGCCTCCCAAAGTAT TGGGATTACAGGCGTGGGCCAACCGCACCCGACCAATTTTTCTGCTT CTTTAAAAACATTTTTTTAAATTTTG 306 patch CGCACCCGACCAATTTTTGTGCTTCTTTAAAAACATTTTTTTAAATTTT GTTTTAGAGACAGGGTCTTGCTCTGTTGCCCAGGCTGGAGTGCAGTG GTGTGATCTCAGTTCACTGCAGCC 307 patch TCTGTTGCCCAGGCTGGAGTGCAGTGGTGTGATCTCAGTTCACTGCA GCCTTGACCTCCTGGGCTCAAGCGATCCTCCCTCCTCAGCCTCCCAA GTAGCTGGGACGACAGGTGCACACCA 308 patch TCAAGACCAGCCTGGGCAAAATTGTGAGGACCCCATCTCTACAAAAA ATTTTAAAATTAGCCAGGCATGGTGGTGTGCACCTGTCGTCCCAGCT ACTTGGGAGGCTGAGGAGGGAGGATC 309 patch GCAGTGGCTCACGCCTGTAATCCCAACACTTTGGGAGGCCGAGGCA GGAGGCTCCCTTGAGCTCAGGAGTTCAAGACCAGCCTGGGCAAAAT TGTGAGGACCCCATCTCTACAAAAAATT 310 patch AGGCTGGTCTTGAACTCCTGAGCTCAAGGGAGCCTCCTGCCTCGGC CTCCCAAAGTGTTGGGATTACAGGCGTGAGCCACTGCACCCAGCCA CCTGGTCTGCGTCTTAAAAGCCTTCCTG 311 patch GAGGTGGAATCACTTGAGCCTGCAGTGAGCTGAGATTGTGTCACTGC ATTACAGCCTGGGCAACAGAGGGAGACCCTCTCAAAAAAATAAAAGG CACGCACGCCCCCAAACCTGAAATGA 312 patch AATGCAGTGACACAATCTCAGCTCACTGCAGGCTCAAGTGATTCCAC CTCAGCCTCCCGAGTTGCCTGGATTATAGGCACACACCATCATGCCT GGCTAATTTTTGGGTTTTTGTTTTTT 313 patch TGAGCAACATATTGAGACCTCATCTCTACCAAAAACAACAAAAACAAC AAAAAAAACCCCTAAAAAACACAAAAAACAAAAACCCAAAAATTAGCC AGGCATGATGGTGTGTGCCTATAA 314 patch TTGTTGTTTTTGTTGTTTTTGGTAGAGATGAGGTCTCAATATGTTGCTC AGGCTGTTCTCCAACTTCTGGGCTCAAGCCATCCTCCTGCCTCCCAA AGTGCTGGGATTACAGATATGAAC 315 patch CAACCCCAAGAATAGAAAAGGCACTCACTGGCCAGTCGAAGTGGTTC ATATCTGTAATCCCAGCACTTTGGGAGGCAGGAGGATGGCTTGAGCC CAGAAGTTGGAGAACAGCCTGAGCAA 316 patch GCTCTGAAGGAAAAGCAGGCCAAGTGGGTTTCTTCCTTTTTTTTTTTT TTTGAGATAGAATCTCTTGCTCTGTCACCCGGGCTGGAGTGCAATGG CACAATCTTGGCTCACTGCAATCTC 317 patch TGTCACCCGGGCTGGAGTGCAATGGCACAATCTTGGCTCACTGCAAT CTCCGCCTCCCGAGTTCAAGCAATTCTCCTGCCTCAGCCTCCTGAGT AGCTGGGATTACAGGCGCGTGACACC 318 patch TTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGATTACAGGCGCGTGAC ACCATGCCTAGCTAATTTGTATATTTTTAGTAGAGACAGGGTTTCA CCATGTTGGTAAGGCTGGTCTTGAA 319 patch TATTTTTAGTAGAGACAGGGTTTCACCATGTTGGTAAGGCTGGTCTTG AACTCCTGACCTCGTGATCCGCTGGCCTCGGCCTCCTAAAGTGCTGG GATTACAGGTGGGAGCCACCGCACC 320 patch TGGCCTCGGCCTCCTAAAGTGCTGGGATTACAGGTGGGAGCCACCG CACCAGGCCTCTTTTTTTTTTTGAGACGGAGTCTTGCTCTGTCGCCCA GGCTGGAGTGCAGTGGCGCGATCTCG 321 patch GACGGAGTCTTGCTCTGTCGCCCAGGCTGGAGTGCAGTGGCGCGAT CTCGGCTCACTGCAAGCTCTGCCTCCTGGGTTCACGCCATTCTCCTG CCTCAGTCTCCCGAGTAGCTGGGACTA 322 patch CCTGGGTTCACGCCATTCTCCTGCCTCAGTCTCCCGAGTAGCTGGGA CTACAGGCACCTGCCACTACGCCTGGCTAATTTTTTGTATTTTTAGTA GAGACACAGTTTCACCGTTTCTACC 323 patch AAGGAATGAGGAGCCCCAGGAGGTCTTGGTAAGAGATAAAAAAACAG GAGGGGGCCCTCTCTGGCTCTATGGTAGAAACGGTGAAACTGTGTCT CTACTAAAAATACAAAAAATTAGCCA 324 patch ACCTGTAATTCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACAA GGTCAGGAGATCGAGACCATCCTGAAGGAATGAGGAGCCCCAGGAG GTCTTGGTAAGAGATAAAAAAACAGGAG 325 patch GACCTTGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGAATTACA GGTATGAGCCACCGCACCCGGCCTTTTTTTTTTTTTTTTGAGAAGCAG TCTCTGTTGCCCAGACTGGAGTGCA 326 patch TTTTTTTTTTTTTTTTGAGAAGCAGTCTCTGTTGCCCAGACTGGAGTG CAGTGGCACGATCTCAGCCCACTGGAACCTCTGCCTCCCGGCTTCAA GCAATTCTCCTACCTTGGCCGCCCA 327 patch TGGAACCTCTGCCTCCCGGCTTCAAGCAATTCTCCTACCTTGGCCGC CCAAGTAGCTGGGATTGCAGGCGCCCACCACCATGCCCAGCTAATTT TTTTTTTTTTTTTTTTTAGACGGAGT 328 patch CCCACCACCATGCCCAGCTAATTTTTTTTTTTTTTTTTTTTAGACGGAG TTTCGCTCTTGTTACCCAGGCTGGAGTGCAAGGGCGCGATCTCGACT CACCACAACCTCCGCCTCCTGGGT 329 patch TGGAGTGCAAGGGCGCGATCTCGACTCACCACAACCTCCGCCTCCT GGGTTCAAGCGATTCTCCTGTCTCAGCCTCCCAAGTAGCTGGGTTTA CAGCCATGTGCCACCACGCCCAGCTAA 330 patch CTGAGGTCGGGAGTTTGAGACCAGCCTGACCAACATGGAGAAACCC CGTTTCTACTAAAAAAATACAAAATTAGCTGGGCGTGGTGGCACATG GCTGTAAACCCAGCTACTTGGGAGGCT 331 patch ACTTGAGGCCAGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTT GGGAGGCTGAGGTGGGCGGATCACCTGAGGTCGGGAGTTTGAGAC CAGCCTGACCAACATGGAGAAACCCCGTT 332 patch AAGAAATAGCCCCTCAGAAACCCACTTGAGGCCAGGCGCGGTGGCT CACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGTGGGCGGATCA CCTGAGGTCGGGAGTTTGAGACCAGCCT 333 patch GGAGGTCAGACTTCAGAAAGGACTTCCCTCTTTTATTTTTTTTTCTGA GACGGAGTCTTGCTCTGTCGCCCAGGCTGGAGTGCAGTGGTACAAT CTCAGCTCACTGCAACCTCCACCTCC 334 patch CAGGCTGGAGTGCAGTGGTACAATCTCAGCTCACTGCAACCTCCACC TCCTGGGTTCAAGCGATTCTTCTGCCTCGGCCTCCCAAGTAGCTGGG ACTACAAGCACCTGCCACCACGCCCG 335 patch TGAGGTCAGTTCCAGACCATCCTGGCCAATATGGTGAAACCCCGTCT CTATTAAAAATACAAAAATAAGCCGGGCGTGGTGGCAGGTGCTTGTA GTCCCAGCTACTTGGGAGGCCGAGGC 336 patch AAGTCCTGGCCGGGTGTGGTGGCTCATGCCTGTAATCCCAGCACTTT GGGAGGCCGAGGTAGGCGGATCATGAGGTCAGTTCCAGACCATCCT GGCCAATATGGTGAAACCCCGTCTCTA 337 patch TGGCCAGGATGGTCTGGAACTGACCTCATGATCCGCCTACCTCGGC CTCCCAAAGTGCTGGGATTACAGGCATGAGCCACCACACCCGGCCA GGACTTCTCTCTTGAGAAGAAAGGGAAA 338 patch TAAAATATGACTTTCGGGGATTGTTATGGTATTAATGAGGTAGTGGCA GGTACATAGTAAGTGCTCAATAAATGGTAGTTCCTCATATTATTGCCC CAGACTATTGCTAACCCTTTCCTT 339 patch TTGTAAGTGGCAGGGCTGAGATCTGAACCCAGTCTGGCTCCTGACCA CAATGTTACACTGCCCCTCAAAATAAAATATGACTTTCGGGGATTGTT ATGGTATTAATGAGGTAGTGGCAGG 340 patch TTGTGGTCAGGAGCCAGACTGGGTTCAGATCTCAGCCCTGCCACTTA CAAGTATTGCGGGTTGGTCAGCCGGGTGCAGTGGCTCACGCCTGTA ATCCTAGCACTTTGGGAGGCCGAGGCG 341 patch TTTTAGTAGAGACAGGGTTTCCCCATGTTGGCCAGGCTGGTCTGGAA CTCCAGACCTTAAGTGATCCCGCCGCCTCGGCCTCCCAAAGTGCTAG GATTACAGGCGTGAGCCACTGCACCC 342 patch TCTCCTGTCTCAGCCTCCCGAGTAGCTGGGATTACAGGCACGTGCCA CCACACCCAGATAATTTTTGAATTTTTAGTAGAGACAGGGTTTCCCCA TGTTGGCCAGGCTGGTCTGGAACTC 343 patch TGGTGGCACGTGCCTGTAATCCCAGCTACTCGGGAGGCTGAGACAG GAGAATCACTTGAACCCAGGAAGCAGAGGTTGCAGTAAGCCGAGAC TGTGCCACTGCACTCCAGCCTGGGCAAC 344 patch TCTAGGGACCCCAACCCAACCCTCAATACTTTTTTTTTTTTTTTTTTTTT TTTAGACAGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGCAGTGGCAC AGTCTCGGCTTACTGCAACCTCT 345 patch CAACAGAGCGAGACTCCGTCTCAAAAAACAAACAAACATTGAACACC CCAACTTCTTCTCAGCGTCTGCTTCTAGGGACCCCAACCCAACCCTC AATACTTTTTTTTTTTTTTTTTTTTT 346 patch AGGAGGCGGAGGTTGTAGGAAGGCGGAGATTGCAGTGAGCCAAGAT CGCTCCACTGCACTCCAGCCTGGGCAACAGAGCGAGACTCCGTCTC AAAAAACAAACAAACATTGAACACCCCA 347 patch AGCGATCTTGGCTCACTGCAATCTCCGCCTTCCTACAACCTCCGCCT CCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGA CTACAGGTGTGCACCACCACACCCAG 348 patch CCTCAGCCTCCTGAGTAGCTGGGACTACAGGTGTGCACCACCACAC CCAGCTAATTTTTGTATTTTTAGTAGAGACAGGGTTTCATCATGTTGG CTAGGATGGTCTCGATCTCTTGACCT 349 patch AGAGACAGGGTTTCATCATGTTGGCTAGGATGGTCTCGATCTCTTGA CCTTGTGATCCGCCCTCCTAGGCCTCCCAAAGTGCTGGTATTACAGG CGTGAGCCACCGCGCCCAGCTCAATG 350 patch CTCCCAAAGTGCTGGTATTACAGGCGTGAGCCACCGCGCCCAGCTC AATGTTTTTTTACAAATCAGCACCTGTGAAAGGAAGGGAGAGGAAAC ATAATTGGGCAGAGGGAGAAGTCAAAC 351 patch GTGCTCAAGCAAGGTGAGGCAATCACAGAGCTCCCCGCCCTTGACC CAGGTTTGTCCAGCCTGTGTTGCTGTTTGACTTCTCCCTCTGCCCAAT TATGTTTCCTCTCCCTTCCTTTCACA 352 patch TCAGCGTCTGCCTCTGGTGCAGACAGCGGCCTCACTGGAAGTCATG CGTTTTCTGGGCAGCCTACACCCAGTGCTCAAGCAAGGTGAGGCAAT CACAGAGCTCCCCGCCCTTGACCCAGG 353 patch CCTTCAAGGAAGGACTTGCCCCAAGCTGCAGGGAGTGCAGGCTGCA GACAGGCTCCAGCTGTCAGCTCCTTCAGCGTCTGCCTCTGGTGCAG ACAGCGGCCTCACTGGAAGTCATGCCTT 354 patch GGAGGTCAAATGACTTGCCCAAGATAACAGGGCTAGTGTTGTAAACA CAGAGATGTGCTGGCCAGATCAGCCTTCAAGGAAGGACTTGCCCCA AGCTGCAGGGAGTGCAGGCTGCAGACA 355 patch CTGTGTTTACAACACTAGCCCTGTTATCTTGGGCAAGTCATTTGACCT CCAAAGCGCCTTGTCTGTAAAAACAGGTAAAATAGTAATGGGATTCAT GGCATTCTTATGAGGATTAAATGA 356 patch ACAGGTAAAATAGTAATGGGATTCATGGCATTCTTATGAGGATTAAAT GAGGTAATATGTGTAAAGCTTTTAACGACACTGCCTGGCACATAGTAA GCATTCAGTACACTGTAAACATGA 357 patch TAACGACACTGCCTGGCACATAGTAAGCATTCAGTACACTGTAAACAT GAACCATTAGTATCTCCACTTTACAACTGAGGCTTAGAGGCAAAGTAG TTTACAAAAGGCCACAAAGTCTGA 358 patch AAGCATTCAGTACACTGTAAACATGAACCATTAGTATCTCCACTTTAC AACTGAGGCTTAGAGGCAAAGTAGTTTACAAAAGGCCACAAAGTCTG ACTTCAATTCCCTTGCCCTAAGCAC 359 patch GGACCCTTCTACCACATACTAAAATTAAAATGGCCCAGGCCGGGTGC AGTGGCTCACACCTATGTGAGCACTTTGGGAAGCCAAGGCAGGTAG ATTACTTGAGGTCAGGAGTTCGAGACC 360 patch CTTTGGGAAGCCAAGGCAGGTAGATTACTTGAGGTCAGGAGTTCGAG ACCAGCCTGGCCAACATGGTGAAACCCCATCTCTTCTAAAAATACAAA AATTAACCCAGTGTGGTGGCATGCA 361 patch ACCCCATCTCTTCTAAAAATACAAAAATTAACCCAGTGTGGTGGCATG CACCTGTAATCCCAAATACTCGGGAGGCTGAGGCATGAGAATCGGTT GAACCCGGCAGGTGGAGGTTGCAGT 362 patch GGAGGCTGAGGCATGAGAATCGGTTGAACCCGGCAGGTGGAGGTTG CAGTAAGCGGAGATCACACCACTGCACTCCAACCTGGGCGACAAAG TGAGACTCAGTCTCAAAAAATAAAATGA 363 patch CACTCCAACCTGGGCGACAAAGTGAGACTCAGTCTCAAAAAATAAAA TGAAATAAAATAAAGTGGCTCAAAGACTCAATTTAAGAGTTAAAACTAT AAAACTCTTAGAAGAAAATATTGT 364 patch AGACTCAATTTAAGAGTTAAAACTATAAAACTCTTAGAAGAAAATATTG TTGAAAATCTTCATCACATTGGACTTGGCAACAACTGCATAAATAGGA TACCAAAAGTACAAGGAAGAAAA 365 patch GACTTGGCAACAACTGCATAAATAGGATACCAAAAGTACAAGGAAGA AAAAATAGTAGGTAAATTGAACTTCATCAAATTAAGAACTTTTGTGCAC CAAAGGACACTATCAAGAAAGTGA 366 patch TCATCAAATTAAGAACTTTTGTGCACCAAAGGACACTATCAAGAAAGT GAAAAAACCTGGAGAATGGAAGAAAATATTTGCAGATCATATATCTAA CAAGGGATTAATATTCAAAATATA 367 patch AAAATATTTGCAGATCATATATCTAACAAGGGATTAATATTCAAAATAT ATATAGAACTCCTACAACTTGACAACAAAAAAACAAACAACCCAATTC AAAAATGGGCAAAGTACTTGAAT 368 patch ACAACAAAAAAACAAACAACCCAATTCAAAAATGGGCAAAGTACTTGA ATAGACACTTCTCCAAAGAAGATATACTAATGGACAATAAATTCGTGG AAATATGCTCAACATCGTTAGTCA 369 patch TTCTTGATTATGGCCATCCTGGTTAGTGTGAAGTGGCATCTCATTGTG GTTGTAATCTGCATTTCCCCAATGACTAACGATGTTGAGCATATTTCC ACGAATTTATTGTCCATTAGTATA 370 patch GTACATTCCCACCAGCAATGCACGGAGGATTCCAATTTCTCCACATC CCCACCAAAACTTATTATCCATTTTCTTGATTATGGCCATCCTGGTTA GTGTGAAGTGGCATCTCATTGTGGT 371 patch GTGACTTGGTAGTTCTATTTTTAACCTTTTGAGGAACTGCCAAACTGT TTTCCCCAATGACTGCACTATTGTACATTCCCACCAGCAATGCACGGA GGATTCCAATTTCTCCACATCCCC 372 patch AAACAGTTTGGCAGTTCCTCAAAAGGTTAAAAATAGAACTACCAAGTC ACCCAGCAATTCCATTCTTAGGCATATATTCAAAAGAAATGAAAGCAG ATATTTGTACACCAGTGTTCACAG 373 patch CATATATTCAAAAGAAATGAAAGCAGATATTTGTACACCAGTGTTCAC AGCTGCACTATTTACAATAGTCAAAAGGTAGAAACAACCTAGGTCCAT CCACAAATGAATGGATAAATAAAA 374 patch AAAAGGTAGAAACAACCTAGGTCCATCCACAAATGAATGGATAAATAA AACGTAGCATATACATACAATGGTACACTAGTCCGCTGTAAAAAGAAA TTTTGATCTTACTGCATGCTACAT 375 patch GTACACTAGTCCGCTGTAAAAAGAAATTTTGATCTTACTGCATGCTAC ATGGCTTCGACATACTACAACATGGATGGACCTTGAAAACATTATTCT TTGTGAAATAAACTAGACACAGGA 376 patch TGGATGGACCTTGAAAACATTATTCTTTGTGAAATAAACTAGACACAG GACAAATGTTAGACGATTCCACTTATATGAGGCACCTAGAATGGGCA ATTTGGTAAGCAAAGTAGAATAGAA 377 patch ATCCCCAACATAAACTCTGTGACCATTAAACAGTAACTCCCCATTCCC TGCTACCTGTGCCCCTAGTAATTTCTATTCTACTTTGCTTACCAAATTG CCCATTCTAGGTGCCTCATATAA 378 patch TCAGTGGCATTAAGTATATTCACAATGTCGTGTACCAATCACCACTCT TTATCCCCGAAACTGTTTCATCATCCCCAACATAAACTCTGTGACCAT TAAACAGTAACTCCCCATTCCCTG 379 patch AAAGAGTGGTGATTGGTACACGACATTGTGAATATACTTAATGCCACT GAATTTTACACTTGAAGTGGTTAAAGCGATAAATATTATAGTTTGCATA TTTTATCATAAAAATATTTTTTT 380 patch AAAGCGATAAATATTATAGTTTGCATATTTTATCATAAAAATATTTTTTT AAACGATGAAGGGACGTGAACGGGTTGAAATTTTATAAAAAGTGGCC AGGGAAGGTGTCACTGCAATGGT 381 patch CGGGTTGAAATTTTATAAAAAGTGGCCAGGGAAGGTGTCACTGCAAT GGTGTCCTACAGGAGGAGGAAGATCATGTGGACATCTGCGGGAAGG GTGTTCTGGCAGAGGGAGTAGCACGGG 382 patch TCATGTGGACATCTGCGGGAAGGGTGTTCTGGCAGAGGGAGTAGCA CGGGCGATGGCTCTGAGGACTGTGAGAAGTATAGTTGGAAACAGCG AGGAGGCCAGGGTGTCCGAAGCTGAGTA 383 patch CTCCTCCTCACTCTCAGCAGAAACTGACCTTCCCCCTCTTATCTCACC TCCTCCCACTCTCTCTGGCTTACTCAGCTTCGGACACCCTGGCCTCC TCGCTGTTTCCAACTATACTTCTCA 384 patch CGTGCACCTGCCACTTCAGCCCCACGGGTCTATAAAATGGGCATGAT TATCGTGGCTACCTCACTGGTCCTGGCAATTAAGGAACAATGTGTGC CAGGCACTCTGTAAACCACATACTTG 385 patch CCCCACGGGTCTATAAAATGGGCATGATTATCGTGGCTACCTCACTG GTCCTGGCAATTAAGGAACAATGTGTGCCAGGCACTCTGTAAACCAC ATACTTGCGAGTGTCAAGCTGGTGAC 386 patch TGTCTGAAAGGACCATTGAAGGGAGCAATTCTTTTTTTTTTTTTTTTTG AAGATGGAGTCTTGCTCTGGACTCCAGGCTGGAGTGCAGTGGTGCG ATCTCAGCTCACTGCAACCTCCACC 387 patch CTCCAGGCTGGAGTGCAGTGGTGCGATCTCAGCTCACTGCAACCTC CACCTCCCAGGTTCAAGCAATTCTCTTGCCTCAGCCTCCCGAGTAGC TGGGACTCCAGGTGCGTGCCACCACGC 388 patch CAGGAGTTTGAGACCAGCCTGGCCAACATGGTGAAACCCCATCTCTA CTAAAAATACAAAAATTAACTGGGCGTGGTGGCACGCACCTGGAGTC CCAGCTACTCGGGAGGCTGAGGCAAG 389 patch CGCTCCCTTTAGGCTGGGTATGGTGTCTCTCAGCACTTTGCGAGGCC AAGGCGGGCAGATCATTTGAGGTCAGGAGTTTGAGACCAGCCTGGC CAACATGGTGAAACCCCATCTCTACTA 390 patch CTTGGCCTCGCAAAGTGCTGAGAGACACCATACCCAGCCTAAAGGG AGCGATTCTATTCTACTATTCTTCCTTCTGCTAATCCTTCCATTCTTTA ATTTAATAACGAAGATTTTTTGAGT 391 patch CTTCTGCTAATCCTTCCATTCTTTAATTTAATAACGAAGATTTTTTGAG TACCTGTCATATACCAGGTGCTGTTCTGGGCCCTGGGAATACAGCTG TTAACAAAATCATCAAACCACTTC 392 patch TGTTCTGGGCCCTGGGAATACAGCTGTTAACAAAATCATCAAACCACT TCCCTCGTGGAGCCCACATTGCAGTGAGAGAGACAAACACGACACA CACTCTCAAGTCCTTGAAGATAAAGA 393 patch AGTGAGAGAGACAAACACGACACACACTCTCAAGTCCTTGAAGATAA AGAAAACTGGGTAACGGAGAGAAGAGGCCAGGGTTTGTTCTATAATC ATTAATAACACGAGCAGTAAGAAGTA 394 patch GAGGCCAGGGTTTGTTCTATAATCATTAATAACACGAGCAGTAAGAA GTAAAATTTATCTAAGTAACAACTTATAAAGGGTCTACTGTGTGCTAA GCTCTCATCCAGGTTCCCAAGGATT 395 patch TTATAAAGGGTCTACTGTGTGCTAAGCTCTCATCCAGGTTCCCAAGG ATTAACTCAGACCACACAGTAATTGAATAGATTCTATCATTGTCATCTT ACAGAGGCCCAGAGAGAGAAAGTG 396 patch CTTGGCCACTAGACCCAAAGTGGCTGAGTTAGAATCCCAGCCCCGTT ACCAGCTATGACACTAGGCAAGTCACTTTCTCTCTCTGGGCCTCTGT AAGATGACAATGATAGAATCTATTCA 397 patch CTCCTCTGTGAGTCCTCTGCGGACCACCCTAGGCAAGCAAAGGGATT AGGAGCTTGGCCACTAGACCCAAAGTGGCTGAGTTAGAATCCCAGC CCCGTTACCAGCTATGACACTAGGCAA 398 patch GGTTCTCAGGGCTGCCTGGGTTCAAACCCCAGCTCCAGACTTTGACT TCCTATGCACCCATTTGAACAAGGTAACCTCTCTGTGCCTCAGCTGTC AGGAGGGTAGAGGAGAGGACTCAAT 399 patch AGCCGAGATCCCGCCACTGCACTCCAGCCTGGGCGACAGAGCGAGA CTCCGTCTCAAAAAAAAAGAACAAGGTTCTCAGGGCTGCCTGGGTTC AAACCCCAGCTCCAGACTTTGACTTCC 400 patch GCCACACCAGCCGGACCACCCGCCAGAGGCTCAACGGCCCCTCCTC GCAGCCGAGGAAACTGAGGCTCGGAGGCAGGGCGCAGAGGCCCAA GGTGACACAGCAGGCGGCCGTCGGCCGGG 401 patch GGCCCGCGCTCCCCGGCCGACGGCCGCCTGCTGTGTCACCTTGGG CCTCTGCGCCCTGCCTCCGAGCCTCAGTTTCCTCGGCTGCGAGGAG GGGCCGTTGAGCCTCTGGCGGGTGGTCCG 402 patch GCAGCAAATCATGGGCTGTCCTAGCCCCTTTTCAGATGAGAAAGGAG CCCAGAGAGGGGAGAGGGCCTGCCAAGGTGGCACATCTGGCCAGG CGCTGCGTAGGCTGAGCCCTGGGGGTCA 403 patch AGACGTCCAGTTTTTTGGGAGGGGTGGGACACAGGAGTCTGTTTTTT AACTAGCTCCCCAGAGCACCTGAGCAGCAAATCATGGGCTGTCCTAG CCCCTTTTCAGATGAGAAAGGAGCCC 404 patch AAGAAATGCAGACGTCCAGTTTTTTGGGAGGGGTGGGACACAGGAG TCTGTTTTTTAACTAGCTCCCCAGAGCACCTGAGCAGCAAATCATGG GCTGTCCTAGCCCCTTTTCAGATGAGA 405 patch GAGGCTGAGGTGGGTGAATCACTTGAGGTCAGGAGTTCGAGACCAG CCTGACCAATATGGTGAAACCCCATCTCAAAAAAAAAAAAAATTGGGG CTAACGGTGAGCCTGTTTTGCAGGAT 406 patch CAGGCTGGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTCAGC CTCCCAAAGTGCTGGGATTATAGGCGTGAGCCACTGCACCCAGCCTA GCCCCATTTTTCACATGAAGAGACCG 407 patch AGGCTGGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTCAGCC TCCCAAAGTGCTGGGATTATAGGCGTGAGCCACTGCACCCAGCCTA GCCCCATTTTTCACATGAAGAGACCGA 408 patch AGGCAGAAGTTGTGATGAGCTGAGATCCCGCCACTGCACTCCAGACT GGGCAACAGAGCAGGACTCTGTAAAAAACAAAACAAAACAAAAAATT ACCCTTCCCCACAATTATAAGCATTT 409 patch CCCAGTCTGGAGTGCAGTGGCGGGATCTCAGCTCATCACAACTTCTG CCTCCTGAGTTCAAGCGATTCTCCTGGCTCAGCCTCTCGAGTAGCTG GGACTAGAGATGCATGCCACCACGCC 410 patch CTGGCTCAGCCTCTCGAGTAGCTGGGACTAGAGATGCATGCCACCA CGCCTGGCTAATTATTTGTATTTTTAGTAGAGATAGGGTTTCTCCATG TTGGTCAGGCTGGTCTCGAACTCCTG 411 patch TAGTAGAGATAGGGTTTCTCCATGTTGGTCAGGCTGGTCTCGAACTC CTGACCTCAAATGATCTGCCCGCCTCGGTCTCCCAAAGTGCTGGGAT TACAGTGAGCCACCACGCCTGTCTGG 412 patch TTGGTCAGGCTGGTCTCGAACTCCTGACCTCAAATGATCTGCCCGCC TCGGTCTCCCAAAGTGCTGGGATTACAGTGAGCCACCACGCCTGTCT GGGTAATTTTTTTTTAAGTATTCTGT 413 patch GGCTGAGCCAGGATGCTGCTGGTGCGCTCGCCGCGCCGGCCCCGC CCTCCCGCGGCCCCGCCCCGCCCGCAGGCCCCGCCCCCGGCAGGC CCCGCCCCGCCGAGCGCCCGGCCGCCCTCC 414 patch CTCGCCGCGCCGGCCCCGCCCTCCCGCGGCCCCGCCCCGCCCGCA GGCCCCGCCCCCGGCAGGCCCCGCCCCGCCGAGCGCCCGGCCGC CCTCCTGTCTGGGCGCGCGTGGCTGGCGGGT 415 patch AGAATGATTGTTGTCGTAAAGGCCTTTGATAATAATAGATACTGTTTA CCCAGTGCTTGATGCCAGGCATTGCTACAAACACTGCGTACACATTA TTCTATTTAATCTTCATAACCCAGT 416 patch TCACTAGCATTTAACCTCTGTGCCCCAGCTTCCTCTTCTGTGAAAGGA CAGTAATGACAGTACCTACCTCACTGGGTTATGAAGATTAAATAGAAT AATGTGTACGCAGTGTTTGTAGCA 417 patch GTGCCAAGTGTGGTACTGCTCTCACTAGCATTTAACCTCTGTGCCCC AGCTTCCTCTTCTGTGAAAGGACAGTAATGACAGTACCTACCTCACTG GGTTATGAAGATTAAATAGAATAAT 418 patch TGTGGAGGGAGGTGGGAAGTTGTGTGGTGTATTGTTTTGAAGGGGTG CTGGAACGAAGTACCACACACTAAGTGGCTTCAACAACCGAAATGTA TGGTCTGTCCTGGTTCTGGAGACTAG 419 patch AGTGGCTTCAACAACCGAAATGTATGGTCTGTCCTGGTTCTGGAGAC TAGAAGTACAAAATCACGGCGTGGGAGGGCTGGCTGCTTCCGAGGC CCATGAAAGAGCATGTGTGCCCGGCCA 420 patch GGAGGGCTGGCTGCTTCCGAGGCCCATGAAAGAGCATGTGTGCCCG GCCACTCTGACTTGCAGATGCCCATCTTCTCCCTATGTCTCCTCACAC CATCTTCCCTGTGGTGTGTGTGTGCA 421 patch TCTTCTCCCTATGTCTCCTCACACCATCTTCCCTGTGGTGTGTGTGTG CAAATCCCTTCTTTCTATAAGGACACCAGTCATACTGGACTAGGGCC CACCCGAATTGCCTCATTTTAACTT 422 patch AGAGGAGTGATAGTGGAGTAGGGGGGAGGGGAATTGGGTGATTTTAA CTTGATGACCTCTGTAATCATGAGGTAATGTCCAAGTAAGGTCCCATT CTAAGATACCTGAATGCCCAGGCAC 423 patch GGTAATGTCCAAGTAAGGTCCCATTCTAAGATACCTGAATGCCCAGG CACGGTGGTTCATGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGC AGGCAGATCAACTGAGGTCAGGAGTTC 424 patch GGAGGATGGGGGGGTAATTTTTTTATTTTTAGTAGAGAGAGGGTTTGA CCATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCAGTTGATCTGC CTGCCTCGGCCTCCCAAAGTGCTGG 425 patch CCTCCACCTCCCTGGGTTCAAACAATTCTTCTGCCTCAGCCTCCCGA GTAGCTGGGACTACAGGTACGCACCACCATGCCCCGCTAATTTTTTT ATTTTTAGTAGAGACAGGGTTTCACC 426 patch TACTCGGGAGGCTGAGGCAGAAGAATTGTTTGAACCCAGGGAGGTG GAGGTTGCAATGAGCCAAGATCACGCCACTGCATTCCAGCCTGGGA GACAGAGCAAGACTCTGTCTCAAAACAA 427 patch TTACGGGTTGAATTGTCACCCCCACATTCCCCAAGTTCATATGTTCAG GGGTTTGTTGTTGTTGTTGTTGTTGTTTTGAGACAGAGTCTTGCTCTG TCTCCCAGGCTGGAATGCAGTGGC 428 patch GGTGAGACAGCCAGTGACGACCATCCACATGTTACGGGTTGAATTGT CACCCCCACATTCCCCAAGTTCATATGTTCAGGGGTTTGTTGTTGTTG TTGTTGTTGTTTTGAGACAGAGTCT 429 patch AGGCTGGGAAAGGCACACAACCCAGTATCAGACCTGAGTTCACACTC CTTCTGGCAGGAACTTCTAGGTGACATTGGGAAGCAACTTCATTCCTT AGAACCTAGATTTCTCCTCAGGCTA 430 patch AAAGAGACCTAAGAGATTATTTAGCCAAGCCCCCTTATAGCCTGAGG AGAAATCTAGGTTCTAAGGAATGAAGTTGCTTCCCAATGTCACCTAGA AGTTCCTGCCAGAAGGAGTGTGAAC 431 patch AGGTATTATTCCTGATTTAAGGAGGATGCAATGAGGCTTGATGTGGAT TCACCCACCCCAAAGCCTGTGTTCTTAACCACTATGCAATACTGCCTC CCATCAAAGTCTCTATCTCAAGTC 432 patch ATTTAATGAGAACGCCAAGGGCGTGGCTGTCAATCCTATGACACCTG TCTGAGGTAGGTATTATTCCTGATTTAAGGAGGATGCAATGAGGCTT GATGTGGATTCACCCACCCCAAAGCC 433 patch GCATGAACCCAGGAGGTAGAGATTGCAGTGAGCCGAGATCGCACCA CTGCACCCCAGCCTGGGCAACAGAGTGAGACTCCGTCTCAAAAAAA GAGACTGGTTTCTTACCTAAGTCACAAA 434 patch GCAGTGGTGCGATCTCGGCTCACTGCAATCTCTACCTCCTGGGTTCA TGCCATTTTCCTGCCTCAGCCTCCCAAGTAGCTGGGACCACAGGCAC CCACCACCACACCCGGCTAGTTTTTT 435 patch CTcGGCTCACTGCAATCTCTACCTCCTGGGTTCATGCCATTTTCCTGC CTCAGCCTCCCAAGTAGCTGGGACCACAGGCACCCACCACCACACC CGGCTAGTTTTTTGTATTTTTAGTAG 436 patch AGCCTGGCCAACATGGTGAAACCCCCTCTCTACTAAAAATACAAAAAT TAGCTGGGCATGGTGGTGGGTGCCTATAATCCCAGCTACTCGGGAA GCTGAGGCAGGACAATCATTTGAACC 437 patch GGTGCAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCGAG GCAGGCGGTCAAGAGTTCGAGACCAGCCTGGCCAACATGGTGAAAC CCCCTCTCTACTAAAAATACAAAAATTA 438 patch CTGCCTCGGCCTCCCAAAGTGCTGAGATTACAGGCATGAGCCACTG CACCAGGCCTGTCTTCAGGTCTTTTTTATTTTATTATTTATTTATTTATT TATTTATTTATTTATTTATTTTGA 439 patch TTTATTTTATTATTTATTTATTTATTTATTTATTTATTTATTTATTTTGAGA CAGAGTCTCGCTCTGTCGCCCAGGCTGGAGTGCCGTGGTGCGATCT CGGCTCACTGCAAGCTCCACCT 440 patch CCCAGGCTGGAGTGCCGTGGTGCGATCTCGGCTCACTGCAAGCTCC ACCTCCCGGGTTCACGCCATTCTCCTGTCTCAGCCTCCCGAGTAGCT GGGATTACAGGCGCCTGCCACCATGCC 441 patch AGGAAATCGAGACCATCCTGGCCAACTTAGTGAAACCCCATCTCTAC TAAAAATACAAAAAAATTAGCTGGGCATGGTGGCAGGCGCCTGTAAT CCCAGCTACTCGGGAGGCTGAGACAG 442 patch GGCCGGGTGCAGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGG CCGAGGCAGGCAGATCACGAGGTCAGGAAATCGAGACCATCCTGGC CAACTTAGTGAAACCCCATCTCTACTAA 443 patch TCGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACTGCACCC GGCCCACATACTACATTTTCTATCCACTCACCAGTTGATGAAGACTTA ATTTGTTTCCAGTTTTCTTTTTTCTT 444 patch CACTCACCAGTTGATGAAGACTTAATTTGTTTCCAGTTTTCTTTTTTCT TTTTTTTGAGATGGGATCTCCCTGTATTGCCCAGGTTGGTCTTGAACT CCTGGGCTCAAGTGATCCTCCCA 445 patch TGAGATGGGATCTCCCTGTATTGCCCAGGTTGGTCTTGAACTCCTGG GCTCAAGTGATCCTCCCACCTAAGCCTCCCAAAGTGCTGGGATTTGT TTCCGGTTTTTTTCCTACTATGCTAT 446 patch TTTTTTTTTTAACCTCTGTACCCCTAGCTTTTTTTTTTTTTTTTTTTTTTT TTGAGATGGATTCTTGCTCTGTCGCCCAGGCTGGAGTGCAGCAGTGT GATCTTGGCTCACTGCAACCTC 447 patch TGTCGCCCAGGCTGGAGTGCAGCAGTGTGATCTTGGCTCACTGCAA CCTCCACCCCCCGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCCAAG TAGCTGGGATTACAGGCGTACGCCACC 448 patch TTGAGACCAGCCTAGCCAACATGGTCAAACCCCGTCTCTACTAAAAA AAATACAAAAATTAGCCAGGCATGGTGGCGTACGCCTGTAATCCCAG CTACTTGGGAGGCTGAGGCAGGAGAA 449 patch CAGTGGCTCACACCTGTAATTCCCAGCACTTTGGGAGGCTGAGGCA GGCGGATCACCTGAGGTTAGGAGTTTGAGACCAGCCTAGCCAACAT GGTCAAACCCCGTCTCTACTAAAAAAAA 450 patch CGCCTGCCTCAGCCTCCCAAAGTGCTGGGAATTACAGGTGTGAGCC ACTGTGCTCAGCCTGTGTGTTTTGAGACAGGGTCTTGCTTCGTCACC CAGGCTGGAGTGCAGTGGCTCAATCAC 451 patch AGACAGGGTCTTGCTTCGTCACCCAGGCTGGAGTGCAGTGGCTCAA TCACAGCTTACTGCAGCCTGGACTTCCCAGGCTCAAGTGATCCTCCC GCCTCAGCCTCTCAAGTAGCTGGAACT 452 patch TCCCAGGCTCAAGTGATCCTCCCGCCTCAGCCTCTCAAGTAGCTGGA ACTACAGGCGAGTGCCACCATGCCTGGCTAAGTTTTAATTTTATGTAG AGATGGTCTCAGTATGTTGCCCAGG 453 patch CTGGCTAAGTTTTAATTTTATGTAGAGATGGTCTGAGTATGTTGCCCA GGCTGATTTCAAACTCTTGGGCCCAAGTGATCCTCCTGCCTTGCTTC CCTCCCAAAGTGCTAGGATTACAGG 454 patch CCAAGTGATCCTCCTGCCTTGCTTCCCTCCCAAAGTGCTAGGATTAC AGGCATGAACCACTTCACCTGGCCCATGCTATATGTTTGCCCCTCGT CTTCTTACCTACTCCCTCAGTTTTCT 455 patch CTTCAGCACAGGAGTTTGGGGAAGACACAAACATTCAACCCCTACTG TTCCAACCCCTGCTTCACAGATGAGAAAACTGAGGGAGTAGGTAAGA AGACGAGGGGCAAACATATAGCATGG 456 patch ATTAATAAGGGCTCCACCCACATCACCTGATGACCTCCCAGAGGTCC TACCTCCAAATACCATCACTCAGCTTCAGCACAGGAGTTTGGGGAAG ACACAAACATTCAACCCCTACTGTTC 457 patch GTAGGACCTCTGGGAGGTCATCAGGTGATGTGGGTGGAGCCCTTAT TAATGGGATTTGTGCCCTTATAGAAAGGGACACAACATGAGATGATCT TGCTCTGGGCCATGCCGGGAGGAAGG 458 patch AAGGGACACAACATGAGATGATCTTGCTCTGGGCCATGCCGGGAGG AAGGGAGAAGGTGGCTGTCAACGAGCCAGGAAGCGGCACTCCTGAC ACTGGATCTACCAACACCCCTATCTCAG 459 patch GCCAGGAAGCGGCACTCCTGACACTGGATCTACCAACACCCCTATCT CAGACTTCCAGCCTCCAGGACCGTGAGAACTGTTTCCTGTTGAAGCC ACCCTCTCTATATTTGTTACAGCAGC 460 patch TGAGAACTGTTTCCTGTTGAAGCCACCCTCTCTATATTTGTTACAGCA GCCCACACTGATTAAGACACTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT GAGATGGAGCCTCGCTCCATC 461 patch TTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGATGGAGCCTCGCTCCATC ACCCAGGCTGGAGTGCAATGGCGCAATCTCGGCTCACTGCAACCTC TGCCTCCCGGGTTCAAGTGATTAT 462 patch GCGCAATCTCGGCTCACTGCAACCTCTGCCTCCCGGGTTCAAGTGAT TATCCTGGGTCAGCCTCCCAAGTAGCTGGGATTGCAGGCACCTGCC ACCATGGCTGGCTAAATTTTGTATTTT 463 patch AGCTGGGATTGCAGGCACCTGCCACCATGGCTGGCTAAATTTTGTAT TTTTAGTAGAGACAGGGTTTCACCATGTTGGCCAGGCTGGTCTCCAA CTCCTGACCTCAGGTGATCCACCTGC 464 patch CATGTTGGCCAGGCTGGTCTCCAACTCCTGACCTCAGGTGATCCACC TGCCTCGGCCTCCCAAAGTGCTGGGCGTGAGCCACCATGCCCGGCC TGACACTTATCTTTTATATCTATATAT 465 patch GGCGTGAGCCACCATGCCCGGCCTGACACTTATCTTTTATATCTATAT ATTTTTTTCTTTGTTGAGACGGAGTCTCACTGTGTCGCCCAGGCTGGA GTGCAGTGGTGTGATCTTGGCTCA 466 patch AGTCTCACTGTGTCGCCCAGGCTGGAGTGCAGTGGTGTGATCTTGG CTCACCGAAACCTCTGCCTCCCAGGTTCAAGTGATTCTCGTGCCTCA GCCTCCGGAGCAGCTGGGATTACAGGC 467 patch GTTCAAGTGATTCTCGTGCCTCAGCCTCCGGAGCAGCTGGGATTACA GGCGTGAGCCACCATGACTGGCCTAAAACACCTACCTTTTATTTTTTA AAAAACCAACACATTATCAGTACTT 468 patch TAAAACACCTACCTTTTATTTTTTAAAAAACCAACACATTATCAGTACT TCATGCCAGACACCATTCTAGGAAATTAACTCCTCTGACTTTCACATC AATCCCATGGGTAGCTGTTATTT 469 patch GAAATTAACTCCTCTGACTTTCACATCAATCCCATGGGTAGCTGTTAT TTACAGATGAGGAAACTGAGGCACAGAGGTAAAACAACTTTGCTGAG GTCACCTTGCTGCTAAGTGACACAG 470 patch ACAGAGGTAAAACAACTTTGCTGAGGTCACCTTGCTGCTAAGTGACA CAGCTGGCATCTAGTGCAGCAGGCTGGCTCCAAGTCTATGCCCCTCA CCCCTCAGACGCTGCTCACCAAGCCG 471 patch AGCCCCTCCGGCTTGGTGAGCAGCGTCTGAGGGGTGAGGGGCATA GACTTGGAGCCAGCCTGCTGCACTAGATGCCAGCTGTGTCACTTAGC AGCAAGGTGACCTCAGCAAAGTTGTTTT 472 patch ATCTTTATTTTTATTAAAGGACAGGGTCTCTGGCCTGGTGCGTTGGCT CACGCCTGTAATCCCAGCACTTTGGGAAGCCAAGGCGGGCGGATCA CGAGGTCAGGAGATTGAGACCATCCT 473 patch TGGGAAGCCAAGGCGGGCGGATCACGAGGTCAGGAGATTGAGACCA TCCTGGCCAACACGATGAAACCCCGTCTCTACTAAAAATACAAAAATT AGCTGGGCGTGGTGGTGAGTGCCTGT 474 patch GTCTCTACTAAAAATACAAAAATTAGCTGGGCGTGGTGGTGAGTGCC TGTAGTCCCTGCTACTCAGGAGGCTGAGGCAGGAGACTTGCTCCTG AACCCAAGAGGCGGAGGTTGCAGTGAG 475 patch CTGAGGCAGGAGACTTGCTCCTGAACCCAAGAGGCGGAGGTTGCAG TGAGCCAAGATCCCGCCACTGCACTCCAGCTTCCCGACAGAGCGAG ACTCTGTCTCACAAAAAAAAAAAAAAAA 476 patch TCCAGCTTCCCGACAGAGCGAGACTCTGTCTCACAAAAAAAAAAAAA AAAAAAAAAAAAAAGTCAGGGTCTCACCCTGTCCGCCAGGCTTGACT GCAGTGGCGTGACCTCAGCTTACTGC 477 patch TCACCCTGTCCGCCAGGCTTGACTGCAGTGGCGTGACCTCAGCTTAC TGCAGCCTCAACCTCCCAGACTCAAGTGATCCTCCCACCTCAGCCTC CTGAGTAGCTGGGACTACAGGTGCAC 478 patch GATACCAGCCTGGACAACATAGCAAGACCCCATCTCTAAAAAAATATA AAAATTAGCCAGGCATAGCAGTGTGCACCTGTAGTCCCAGCTACTCA GGAGGCTGAGGTGGGAGGATCACTT 479 patch CGTGACTCACATCTGTGATCCCAGCACTTTGGCAGGCTGAGGCAGG AGGATCACTGGAGGCCAGGAGCTTGATACCAGCCTGGACAACATAG CAAGACCCCATCTCTAAAAAAATATAAA 480 patch CAGGCTGGTATCAAGCTCCTGGCCTCCAGTGATCCTCCTGCCTCAGC CTGCCAAAGTGCTGGGATCACAGATGTGAGTCACGTGCTTGGCCTAA ACTTTTAAATGATGAGACTTAAGTCA 481 patch CTCAGTTTCCCCTTTTGTAAAATAGGATGATGATACTTGCACCTCAAG GTGCTGGGAGGATTCACTGTGAGCATGTGAGAAGCAGAGGGCAGAC TGTGGTGGCTGGTGGGCCAGGGCAGA 482 patch CACACCTGCGCTCCAGCCTGGGTGACAGAGCGAGACTCCGTCTCAA AAAAAAATAAAAATAAAAAATAAACTCAGTTTCCCCTTTTGTAAAATAG GATGATGATACTTGCACCTCAAGGT 483 patch TTTTTTGAGACGGAGTCTCGCTCTGTCACCCAGGCTGGAGCGCAGGT GTGCGATCTCGGCTCACTGCAACCTCCACCTCCTGGGTTCAAGCGAT TCTCCTGCCTCAGCCTCCTGAGTAGC 484 patch CGGTGAAACCCCATCTCTACTAAAAATACAAAAAATTAGCTGGGTGTG GTGGTGTGTGCCTGTAGTCCCAGCTACTCAGGAGGCTGAGGCAGGA GAATCGCTTGAACCCAGGAGGTGGAG 485 patch ATCCCAGCACTTTGGGAGGCCGAGGCGGTCGGATCACGAGGTCAGG AGATCAAGACCATCCTGGCTAACACGGTGAAACCCCATCTCTACTAA AAATACAAAAAATTAGCTGGGTGTGGT 486 patch CCTGGGCAAATCACTTCCTTTCTTTAAATTCAGTTTCCCCTTTTGCCG GGCGCGGTGGCTCATGCTTGTAATCCCAGCACTTTGGGAGGCCGAG GCGGTCGGATCACGAGGTCAGGAGAT 487 patch GGGTCTGCAGGCTGGGTGGACCCCAAGCTTAGTTGGATCCTGGGCA AATCACTTCCTTTCTTTAAATTCAGTTTCCCCTTTTGCCGGGCGCGGT GGCTCATGCTTGTAATCCCAGCACTT 488 patch CCCGGCCTGGGGGGTCAGGAGGGCTTCCTGGAAGAGGGGGTATCC TGAGCCCTGGAAGAGGAGACACCAGCCAGGCTGCTAGAGGCTGGG GATCCCCAGCACACAGGCTCCAGGCTGGGC 489 patch TAGCAGCCTGGCTGGTGTCTCCTCTTCCAGGGCTCAGGATACCCCCT CTTCCAGGAAGCCCTCCTGACCCCCCAGGCCGGGCAGCCACTCCAG GGCTCCTCAGTTCAGCAATGTGTCTCT 490 patch TTCAAGTGATTCTTCTTGCCTCAGCCTCCCAAGTAGCTGGGATTACAG GCACCCACGACCATGCCCGGCTAATTTTTGTATTTTTAGTAGAGACAG GGTTTCACCATATTGGCCAGGCTG 491 patch AATTTTTGTATTTTTAGTAGAGACAGGGTTTCACCATATTGGCCAGGC TGGTCTCGAACTCCTGACCTCGTGATCCTCCTGCCTTGGCCTCCCAA AGTGTTGGGATTACAGGCATGAGCC 492 patch TGATCCTCCTGCCTTGGCCTCCCAAAGTGTTGGGATTACAGGCATGA GCCACCGTGCCCGGCCTAATTTTTGTATTTTTTAGTAGAAACAGGGTT CCACCATGTTGGTCAGGCTGGTCTT 493 patch TGTATTTTTTAGTAGAAACAGGGTTCCACCATGTTGGTCAGGCTGGTC TTGAGGTCCTGACCACAGGTGATCTGACCTCGCCTTGGCCTCGAAAA GTGCTGGGATTATAGGCATGAGCCA 494 patch TCTGACCTCGCCTTGGCCTCGAAAAGTGCTGGGATTATAGGCATGAG CCACCGCACCCCACACCAACCTAGAAAAGTTCAACTCATTTGTCTAA GCCCAGCAAAATCATCCAGAAGCCGG 495 patch GAAAAGTTCAACTCATTTGTCTAAGCCCAGCAAAATCATCCAGAAGCC GGTGGCGGTGGCTCACACCCATAATGCCAGCACTTTGGGAGGCTAA GACATGAGGATCACTTGAGGCCAAGA 496 patch AATGCCAGCACTTTGGGAGGCTAAGACATGAGGATCACTTGAGGCCA AGAGTTTGAGACCAGCCTGAGAAATATAGCAAGACCCCCGTCTCTAT GAAAAATACAAAAATTAGTTGGGTGC 497 patch ATATAGCAAGACCCCCGTCTCTATGAAAAATACAAAAATTAGTTGGGT GCGGCGGCATGTGCCTGTGGTCCCAACTACTCTGGAGACTGAGGCA GGAGGATCACTTGAGGCCAGGAGCTT 498 patch CCAACTACTCTGGAGACTGAGGCAGGAGGATCACTTGAGGCCAGGA GCTTGAGGCTGCAGTGATCTGTGATGGTGCCACTGCACTCCAGCCA GGGCGACAGAATGACACTGTCTCAAAAA 499 patch TGGTGCCACTGCACTCCAGCCAGGGCGACAGAATGACACTGTCTCA AAAAAAAATGTCGGCTGGGCGCGGTGGCTCACACCTGTAATCCCAG CACTTAAGGAGGCTGAGGTGGGCGGATC 500 patch TGGCTCACACCTGTAATCCCAGCACTTAAGGAGGCTGAGGTGGGCG GATCACGAGGTCAGGAGATCGAGACCATCCTGGCTAACACGGTGAA ACCCCGTCTCTACTAAAAATACAAAAAA 501 patch CCATCCTGGCTAACACGGTGAAACCCCGTCTCTACTAAAAATACAAAA AATTAGCCTGGCGTGGTGGCGGGCGCCTGTAGTCCCAGCTACTCGG GAGGCTGAGGCAGGAGAATGGCATGA 502 patch GCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGC ATGAACCCGGGAGGCGGAGCTGGCAGTGAGCCGAGATCGTGTCACT ACACTCTAGCCTGGATGACAGGGCCAGA 503 patch AGGCGGAGCTGGCAGTGAGCCGAGATCGTGTCACTACACTCTAGCC TGGATGACAGGGCCAGACTCCATCTCAAAAAAAAAAAAAAAAAAATCA TCTAGTGGTGATGGGACTTTGTAGGG 504 patch GGAGAATTACAGCCCCCATCATAGTGTGTTGGGGTAAGAATTAAGTG AGTTCCCATATATGGGACAAACTTCCCCCCCTTATGACCTGTAAACCC AGTTTCTGGCGGCCAAGGATGGGGA 505 patch GCACTCCAGCCTGGGTGACAGAGTGAGACTCCATCTCAAAAATAAAA TCAATAAAATAAAGTAAAATGAGGGAGAATTACAGCCCCCATCATAGT GTGTTGGGGTAAGAATTAAGTGAGT 506 patch TGATTTTATTTTTGAGATGGAGTCTCACTCTGTCACCCAGGCTGGAGT GCAATGGCATGAACTTGGCTCACTGCAACCTCTGACTCCCAGGTTCA AGAGATTCTCTTGCCTCAGCCTCCT 507 patch CTGCAACCTCTGACTCCCAGGTTCAAGAGATTCTCTTGCCTCAGCCT CCTCAGTAGCTGGAACCACAGGCGCCCGCCACCACACCTGGCTAAT TTTTGTATTTTTAGTACAGACTGGGTT 508 patch GCCCGCCACCACACCTGGCTAATTTTTGTATTTTTAGTACAGACTGGG TTTCACCGTGTTGGCCAGGCTGGTCTCAAACTCCTGACTTCAAGTGA TCCGCCTGCCTTGGCCTCCCAAAGT 509 patch GTCTCAAACTCCTGACTTCAAGTGATCCGCCTGCCTTGGCCTCCCAA AGTGCTAGGATTACAGGTGTGAGCCACCATGTCCAGTCCTCTCCCCA TTTTATAGGTGAGGAGACTGAGGCTC 510 patch CCACCATGTCCAGTCCTCTCCCCATTTTATAGGTGAGGAGACTGAGG CTCAGAGAAGTAAAGCTACTCACCTAAGATCCCACAGCCTTCAAGCG GCAGAGCTGGGATTTGAACCTCGGCC 511 patch TACTCACCTAAGATCCCACAGCCTTCAAGCGGCAGAGCTGGGATTTG AACCTCGGCCATCTGGGTGTGGAGCCTTATTATTCACCACTTTGGCA GGTGTCTCAGTGGCTTACTTACCCTT 512 patch CCCAGCTCATGCAGTCATTTATTCATTCAACAAGCATCACCCACGCTG GGCCCCCAAGAGGCCTCAGCCCTGACCAGGTCCTCAAGGAGCTATC TTAAGAGAGGACAGAGCTGGACATAG 513 patch TGACCAGGTCCTCAAGGAGCTATCTTAAGAGAGGACAGAGCTGGACA TAGACACTCCTAGTCCCATGCAGTTAAGGAAGGTCCAGAGGGAAAGA CAGGGTCCTGGAAGGCTTCCTGGAGG 514 patch CCAATGATAGGTTTGGGGAATCTTAGTGAACTCCTACTCATGCGTTGA AGCCCCAACTGTAATGCCTCCTCCTCCAGGAAGCCTTCCAGGACCCT GTCTTTCCCTCTGGACCTTCCTTAA 515 patch TTGGAGAGCCAATGATAGGTTTGGGGAATCTTAGTGAACTCCTACTC ATGCGTTGAAGCCCCAACTGTAATGCCTCCTCCTCCAGGAAGCCTTC CAGGACCCTGTCTTTCCCTCTGGACC 516 patch CCTCTGTCCTTCACATCGCCAAACTCCAAGAAATGGTCAAAGGCTTT GAACGGAGACCTTGAAGAAAAAGCGGGAAACTGCTTTTCAACATGTC CAGAGATGCTCATTCTTGCCAGGTGC 517 patch CGGGAAACTGGTTTTCAACATGTCCAGAGATGCTCATTCTTGCCAGG TGCAGTGGCTTACACCTGTAATCCCAACACTTTGGGAGGCTGAAGTG AGCAGATCGCTTGAGCCCAGGAGTTC 518 patch CCAACACTTTGGGAGGCTGAAGTGAGCAGATCGCTTGAGCCCAGGA GTTCGAGACCAGCCTGGCCATCATGGTGAAACCCCGTCTCTACTTTA AAAAATACAAAAATTAGCCAGGTGTGG 519 patch GGTGAAACCCCGTCTCTACTTTAAAAAATACAAAAATTAGCCAGGTGT GGTGGTATGTGCCTGTAGTCCCAGCTACTCAGGAGGCTGAGGCAGG AGAATTGTTTGAACCCAGGAGGTGGA 520 patch AGCTACTCAGGAGGCTGAGGCAGGAGAATTGTTTGAACCCAGGAGG TGGAGGCTGCAGTGAGCCAAGATCACTCCACTGCATTCCAGCCTGG GCAACAGAGTGAGACCTGTCTCAAAAAA 521 patch ACTCCACTGCATTCCAGCCTGGGCAACAGAGTGAGACCTGTCTCAAA AAAAAAAAAAAGTTCACACTTAATAAGAAAACTGCAAATCACAAACTG TTTGTCTTCACCAATCAAATTGGCA 522 patch CACCAGTGCTACACCATGGACGCACCCCACAGCCTGGCTGGCACAG AATGTCATTGCATTGTTGGATTTTTGCCAATTTGATTGGTGAAGACAA ACAGTTTGTGATTTGCAGTTTTCTTA 523 patch CAGAAGTGGACTTGCTGTGTCAGCAGGCACATGAGTTTATCATTCCG GTGGCCTGTGCCAGGGTGCCCTCCACCAGTGCTACACCATGGACGC ACCCCACAGCCTGGCTGGCACAGAATG 524 patch CACCGGAATGATAAACTCATGTGCCTGCTGACACAGCAAGTCCACTT CTGGGAATCCCTGCCTGAATATTTGCATGTTTACAGTGTGAACTGACT AACGAATAAAAAAATGTGGCTCAGC 525 patch CTGACCTCGTGATCCGCCCACCTTGGTCCCCCAAAGTGCTGGGATTA CAGGCATGAGCCACCACGTCCAGGCTGAGCCACATTTTTTTATTCGT TAGTCAGTTCACACTGTAAACATGCA 526 patch TGCCCAGCTAATTTTTGTATTTTTAGTGGAGAGGGGGTTTCACCATGT TGGCCAGGCTGGTCTGGTACTCCTGACCTCGTGATCCGCCCACCTT GGTCCCCCAAAGTGCTGGGATTACAG 527 patch CAACATGGTGAAACCCCGTCTCCACTAAAAATACAAAAATTAGCTGG GCATGGTGGCACGTGCCTGTAATCCCAGCTACTAGGGAGGCTGAGG CAGGAGAATCGCTTGAACCCAGGAGGC 528 patch CCCAGCTACTAGGGAGGCTGAGGCAGGAGAATCGCTTGAACCCAGG AGGCAGAGGTTGCAGTGAGCTGAGATCATGCCACTGCACTCCAGTTT GGGCGTTAGAGCGAGACTCCATCTCAA 529 patch ATCATGCCACTGCACTCCAGTTTGGGCGTTAGAGCGAGACTCCATCT CAATAATAATAATAATAATAATAATAATAATAATTTAAAAATTAGCTGGG CATGGTGGCTTCAGCCTGTAGTC 530 patch ATAATAATAATTTAAAAATTAGCTGGGCATGGTGGCTTCAGCCTGTAG TCCCAGCTACTTCAGAGGCTGAGGTGGGAGGATCCCTTGAGCCCAG AAGGTTGTGACTGCAGTGAGCCGTGA 531 patch GGTGGGAGGATCCCTTGAGCCCAGAAGGTTGTGACTGCAGTGAGCC GTGATTGTGCCACTCCACTCCAGCCTATGCAGCAGAGCAAGACCCTA TCTCTAAAAAATAATTTAAAATAAATG 532 patch CTATGCAGCAGAGCAAGACCCTATCTCTAAAAAATAATTTAAAATAAA TGGCTGGGCCGGCCGCGGTGGCTCATGCCTGTAATCCCAGCACTTT GGGAGGCTGAGGTGGGCGGATCACCT 533 patch TCATGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGTGGGCGGATC ACCTGAGGTCCAGAGTTTGAGACTAGCCTGACCAACGTGGAGAAACT CCATCTCTACTAAATACACAAAATTAG 534 patch AGCCTGACCAACGTGGAGAAACTCCATCTCTACTAAATACACAAAATT AGCCGGGTGTGGTGGCGCATGCCTGTAATCCCAGCTACTTGGGAGG CTGAGGCAGGAGAATCACTTGAGCCT 535 patch CTGTAATCCCAGCTACTTGGGAGGCTGAGGCAGGAGAATCACTTGAG CCTGGGAGGTAGAGTTTGCAGTTGAGCCGAGATCACGGCACTGCAC TCCAGCCTGGGCAACAAGAGCAAAACT 536 patch GAGCCGAGATCACGGCACTGCACTCCAGCCTGGGCAACAAGAGCAA AACTCCATCTCAAAATAATAATAATAAATAAATAAATTGGCTAAAATGT TCAATTTTATGTTGTGTGTATGTTG 537 patch TAAATAAATAAATTGGCTAAAATGTTCAATTTTATGTTGTGTGTATGTT GCAGGTTTGTTTTTTTGAGAAGGCAAAGTCAGGCGTGGTGGCTCACA CCTGTAATCCCAGCACTTTGGGAG 538 patch GGCAAAGTCAGGCGTGGTGGCTCACACCTGTAATCCCAGCACTTTG GGAGGCTGAGGTGGGCGGATCACAAGGTCAGGAGACTGAGACAATC CTGGCCAACGCTGTGAAACCCTGTCTCT 539 patch AGGTCAGGAGACTGAGACAATCCTGGCCAACGCTGTGAAACCCTGT CTCTACCAAAAATACAAAAAATTAGCTGGGCGTGGTGGCATGTACCT GTAATCCCAGCTACTCGGGAGGCTGAG 540 patch GCTGGGCGTGGTGGCATGTACCTGTAATCCCAGCTACTCGGGAGGC TGAGGCAGGAAAATCACTTGAACCAGGGAGTTGGAGGTTGCAGTAA GCCTAGATCGCGCCACAGCACTCCAGCC 541 patch TCACTTGAACCAGGGAGTTGGAGGTTGCAGTAAGCCTAGATCGCGC CACAGCACTCCAGCCTGGTGACAGAGCGAGACTTCATATAAAAAAAA AAAAGAGAGAGAGAGAGAAGGCAAAAA 542 patch TACTAAAAATACAAAAAAATTAGCTGGGCATGGTGGCGGGCGCCTGT AGTCCCAGCTACTTGGGAGGCTGAGGCAGAAGAATGGCTTGAACCC GGGAGGTGGAGCTTGCAGTGAGCTGAG 543 patch AGGCAGAAGAATGGCTTGAACCCGGGAGGTGGAGCTTGCAGTGAGC TGAGATTGCGCCACTGCACTCCAGCCTGAGCGACAGAGCGAGACTC CATCTCAAAACAAAACAAACAAACAAAA 544 patch CTGCACTCCAGCCTGAGCGACAGAGCGAGACTCCATCTCAAAACAAA ACAAACAAACAAAACAAAACAAAACAAAACAAAACAAAAAAAGATTCC TTTGGCTACCTGGGTGGGTAGCCCA 545 patch CTTCACAAGATGCAATGAAGAAGTGGGCTTTTTTTTTTTTTGAGACAG AGTTTCTCTCTTGTCACCCAGGCTGGAGTGCCATGGCGCAATCTCAG CTCACTGCAACCTCCACTTCCCGGG 546 patch CTGGAGTGCCATGGCGCAATCTCAGCTCACTGCAACCTCCACTTCCC GGGTTCAAGCGACTCTCCTGCCTCAGCTACCTGGGTGACTGGGATTA CAGGCTTGCGCCACCATGCCCGGCTA 547 patch CTGAGGTCAGGAGTTTGAGACCAGCCTGACCAACATGGAGAAACCC CGTCTCTACTAAAAATACATAAATTAGCCGGGCATGGTGGCGCAAGC CTGTAATCCCAGTCACCCAGGTAGCTG 548 patch ACTTCTGGCCGGGTGTGGTGGCTCATGCCTGTAATCCCAGCACTTTG GGAGGCTGAGGCGGGTGGATCACCTGAGGTCAGGAGTTTGAGACCA GCCTGACCAACATGGAGAAACCCCGTC 549 patch TCCCAAAGTGCTGGGATTACAGGCATGAGCCACCACACCCGGCCAG AAGTAGGCCTTTACCCACTACATGCCTTCTTTTACTTATCTGCACAAT GAAGATTAAAAATAGTTTCTTGGCCT 550 patch CCTTCTTTTACTTATCTGCACAATGAAGATTAAAAATAGTTTCTTGGCC TGGCATGGTGCCTCACACCTGTAATTCCAGCACTTTGGGAGGCTGAG GTGGGCAGATCATTTGAGGTCAGA 551 patch TAATTCCAGCACTTTGGGAGGCTGAGGTGGGGAGATCATTTGAGGTC AGAAGTTCAAGACCAGTGTGGCCAACGTGGCGAAACCCCATCTCTAC TAAAAATACAAAAAGTAGCCAGGCAT 552 patch AACGTGGCGAAACCCCATCTCTACTAAAAATACAAAAAGTAGCCAGG CATGGTGGCACGTGCCTGTAGTCCCAGACACTCAGGAGACTGAGGC ACAAGAATCTCTTGAACCTGGGAGATG 553 patch TTTGAGACAGAGTCTTGCTCTGTCCCCCAGGCTGGAGTGCAATGGCT CGATGTCAGCTCACTGCAACCTCCATCTCCCAGGTTCAAGAGATTCT TGTGCCTCAGTCTCCTGAGTGTCTGG 554 patch GTATCAATTAAACATGGAGCAATTTAATTCTCACAGTAACCCTATGATA AGAGACTTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGCTCTGTCCCCC AGGCTGGAGTGCAATGGCTCGA 555 patch TTATCATAGGGTTACTGTGAGAATTAAATTGCTCCATGTTTAATTGATA CATGATAAACTGATACTTAGCACAGGGCCTAGTAAATATCAGTGCTCT AGTAGTGCCTGCCCATATTATTA 556 patch ACAGGGCCTAGTAAATATCAGTGCTCTAGTAGTGCCTGCCCATATTAT TATCATTGTTTGTGTCATTTATCTCTGTAGTAGGAAGTATATACAATCC TATTGCATAGGTTTAAGGGAATT 557 patch CTCTGTAGTAGGAAGTATATACAATCCTATTGCATAGGTTTAAGGGAA TTAATCCACTAAAGTGTTTGGAACAGAGCCTGGCACATATTGCTATGT AACTGCATCATCATCATCATCCCT 558 patch ACAGAGCCTGGCACATATTGCTATGTAACTGCATCATCATCATCATCC CTTTTTAATAGATGAGAAAACTGAATTTCAGAGAGGGTAGTCTGATCT GAAATTCACCTATTATTCCAGCTT 559 patch AACTGCATCATCATCATCATCCCTTTTTAATAGATGAGAAAACTGAATT TCAGAGAGGGTAGTCTGATCTGAAATTCACCTATTATTCCAGCTTCTC TCTTCCAAATACGGCCTCTGTGC 560 patch AGAATTCTCATTCAGAACCTTGATCACAGGCCGGGCGCGCCGGGATT GCTCACGCCTGTAATCCCAACACTTTGGGAGGCCGAGGTGGGAGGA TCACTTGAGCCCAGGATTTGGAGACTA 561 patch TTTGGGAGGCCGAGGTGGGAGGATCACTTGAGCCCAGGATTTGGAG ACTAGCCTGGGCAACATAGCGAGACCCCTTCTCTAAAAAAGCAAACA GGCAAAACTTCATGAGAATCTTGATCA 562 patch CCCCTTCTCTAAAAAAGCAAACAGGCAAAACTTCATGAGAATCTTGAT CATGTTAAAATTTTATGTCCTTCGATTTCTCCCTACACACACACACACA CACACACACACACACACACACAC 563 patch TGAGAATCTTGATCATGTTAAAATTTTATGTCCTTCGATTTCTCCCTAC ACACACACACACACACACACACACACACACACACACACACACTCAAC ATTTCCTCCACCCATATCATCACT 564 patch TAGTTTTATCCTGTTTTCCGAAAAACAATCATTTATTTATTTATTTATTT ATTTAATTTTATGAGACAGGGTCTGGCTTTGTCACCCAGGCTGGAGT GCAGTGGTGCGATCTTGGCTCAC 565 patch GTCTGGCTTTGTCACCCAGGCTGGAGTGCAGTGGTGCGATCTTGGC TCACTGCAACCTCTGCCTCTCAGATTCAAGCCATCCTTCCACCTCAG CTCTGCCACTGAGTAGCTGAGACTACA 566 patch TTCAAGCCATCCTTCCACCTCAGCTCTGCCACTGAGTAGCTGAGACT ACAAGCACTCGCCACCATGCCCGGCTAATTAAAAAAATAATAATCATT TTAAATGCAAGCTTTATATTATAAA 567 patch GGTAATTAAAAAAATAATAATGATTTTAAATGGAAGGTTTATATTATAAA TACAAAGTAAACATGAAAATAAAACCCAAACATAGCAGTGTTATTAAA CTCTGGCCTGTAGCAGTGGCTC 568 patch AAAACCCAAACATAGCAGTGTTATTAAACTCTGGCCTGTAGCAGTGG CTCACACCTGTAATCCTAGCAGTTTGGAGGCCGAGACAGGTGGATTA CTTGAGACCTGGAGTTTGAGACCAGC 569 patch TTGGAGGCCGAGACAGGTGGATTACTTGAGACCTGGAGTTTGAGAC CAGCCCAGGTGACACAGCAAGACCTCATCTCTACTAAAAATAAAAAAA AATTAGCCAGGTGTGGTGGTATGCAC 570 patch TCATCTCTACTAAAAATAAAAAAAAATTAGCCAGGTGTGGTGGTATGC ACCTGTGGTCCCAGCTACTTAGGATGCTGGAGTGCGAGGATCGCTT GAGCCCAGGAGGTCAAGGCTGCAGTG 571 patch GATGCTGGAGTGCGAGGATCGCTTGAGCCCAGGAGGTCAAGGCTGC AGTGAACTATGATCACTCATTACACCCCAGCCTGGGTGACAGAGCGA GATGCTGTCTCAAAACAAAACAAAACG 572 patch CCCCAGCCTGGGTGACAGAGCGAGATGCTGTCTCAAAACAAAACAAA ACGAAAAACAACTCTGGCTAGATGCTATTGCTTGCCAAGGGTGCAGT CTTCCATTTATTAAAAGTGAAAATTA 573 patch GCTATTGCTTGCCAAGGGTGCAGTCTTCCATTTATTAAAAGTGAAAAT TAGGGCCAGGCACATTGGCTCATGCCTGTAATCCCAGCACTTTGGGA GGCTGAGGTGGGTGGATCACCTGAG 574 patch TGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGTGGGTGGATCACC TGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACCTTA TCTCTGCCAAAAATATAAAAGATTAGC 575 patch CTGGCCAACATGGTGAAACCTTATCTCTGCCAAAAATATAAAAGATTA GCCATGTGTCGTGGTGGGTGCTTGTAATCTCAGCTACTTGGGAGGCT GAGGCAGGAGAATCACTTGAACCCA 576 patch TGTAATCTCAGCTACTTGGGAGGCTGAGGCAGGAGAATCACTTGAAC CCAGGAGGCAGAGGTTGCAGTGAGCCAAGATTGTGCCATTGCACTC CAGCCTGTGCAACGAGCGAAACTCCAA 577 patch TCAGCTACTTGGGAGGCTGAGGCAGGAGAATCACTTGAACCCAGGA GGCAGAGGTTGCAGTGAGCCAAGATTGTGCCATTGCACTCCAGCCT GTGCAACGAGCGAAACTCCAACTCAAAA

APPLICATION

Profiling of ctDNA may offer a non-invasive approach to estimate disease burden and monitor disease progression. Embodiments of the method described herein provide a quantitative method, which exploits local tissue-specific and gene-specific cfDNA degradation patterns, that can accurately estimate ctDNA burden independent of genomic aberrations.

Nucleosome-dependent cfDNA degradation at selected NDRs (e.g. promoters and first exon-intron junctions) is shown herein to be strongly associated with differential transcriptional activity in tumors and blood. A machine learning model that was developed based on expression-specific DNA degradation patterns was found to be capable of accurately predicting ctDNA fractions (see examples). Leveraging on these findings, embodiments of the methods enable for the first time the detection of tumor DNA burden (even of very low frequency) in blood by only sequencing selected NDRs in cfDNA assays. From only less than 50 kb DNA sequence in total (4 kb×6 features or 4 kb×10 features), embodiments of the methods can accurately predict ctDNA levels, and thereby monitor the dynamics of the systemic tumor burden over time from blood/liquid samples. Indeed, using compact targeted sequencing (<25 kb) of predictive regions, the disclosure demonstrates how embodiments of the method enable quantitative low-cost tracking of ctDNA dynamics and disease progression.

Embodiments of the method enjoy several advantages including cost efficiency, flexibility, high accuracy and high sensitivity.

Embodiments of the method requires less sequencing and are therefore cost-efficient. In embodiments of the method, 100× less DNA sequencing (e.g. ˜30 kb at 100× coverage) is needed than low-pass WGS-based methods requiring whole genome sequencing at ˜0.1×. The sequencing cost is also comparable to sequencing a panel at 10,000× (usual target for coding mutation panels). Embodiments of the method also require less sequencing than standard targeted sequencing assays, which usually require more than 1000 kb DNA sequence.

Further, embodiments of the method can be implemented as an extension/add-on to a standard targeted panel assay, providing flexibility and further allowing for an extremely cost-effective approach to generic ctDNA profiling. For example, the NDRs identified herein can be easily added to existing cfDNA capture panels, eliminating the need to perform two separate assays. Notably, WGS or methylation-based assays do not enjoy this flexibility.

Last but not least, embodiments of the method are capable of accurately estimating cancer cell-free DNA burden with a mean deviation of about 3.4%. As compared to conventional coding panel that usually fail (no mutations) in more than 20-30% of patients, embodiments of the method are shown to be able to accurately predict cancer cfDNA in most cancer patients. As demonstrated in the examples, both colorectal cancer and pan-cancer models have high prediction accuracy, with the pan-cancer model generalizing well to most/all solid tumor types.

Overall, embodiments of the method enable quantitative low-cost tracking of ctDNA dynamics and disease progression, and would be invaluable in the clinical setting.

It will be appreciated by a person skilled in the art that other variations and/or modifications may be made to the embodiments disclosed herein without departing from the spirit or scope of the disclosure as broadly described. For example, in the description herein, features of different exemplary embodiments may be mixed, combined, interchanged, incorporated, adopted, modified, included etc. or the like across different exemplary embodiments. The present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive. 

1. A method of estimating a circulating tumor DNA (ctDNA) burden in a subject, the method comprising: determining in a blood sample obtained from the subject, a level of cell-free DNA (cfDNA) that maps to one or more nucleosome-depleted region (NDR); and estimating the ctDNA burden based on said level of cfDNA, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood sample and tumor sample and/or (ii) is degraded to different extents between cfDNA in healthy blood sample and cfDNA in blood sample of a tumor-bearing subject.
 2. The method according to claim 1, wherein determining in a blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR comprises: sequencing cfDNA fragments in the blood sample to obtain sequencing reads; and determining the number of sequencing reads that align with the one or more NDR to obtain said level of cfDNA that maps to one or more NDR.
 3. The method according to claim 2, further comprising contacting the blood sample with one or more probe capable of binding to the one or more NDR to capture cfDNA fragments comprising the one or more NDR prior to the sequencing.
 4. The method according to claim 1, wherein the NDR is selected from the group consisting of: a promoter region, a first exon-intron junction and combinations thereof.
 5. The method according to claim 1, wherein the estimated ctDNA burden is positively associated with a tumor burden in the subject.
 6. The method according to claim 1, wherein said transcript that is differentially expressed between healthy blood sample and tumor sample comprises a transcript which FPKM (Fragments Per Kilobase of transcript per Million), or RPKM (Reads Per Kilobase Million), or TPM (Transcripts Per Kilobase Million) value differs between healthy blood sample and tumor sample, optionally wherein the value differs by at least 10 times between healthy sample and tumor sample.
 7. The method according to claim 1, wherein said NDR that is degraded to different extents between cfDNA in healthy blood sample and cfDNA in blood sample of a tumor-bearing subject comprises a NDR having different sequencing coverage in healthy blood sample and in tumor sample.
 8. The method according to claim 1, wherein said transcript that is differentially expressed in healthy blood sample and tumor sample is selected from the group consisting of: a transcript that is more highly expressed in healthy blood sample than in tumor sample, a transcript that is more highly expressed in tumor sample than in healthy blood sample and combinations thereof.
 9. The method according to claim 1, wherein said transcript which is differentially expressed between blood sample and tumor sample consists of transcript(s) that is more highly expressed in blood sample than in tumor sample.
 10. The method according to claim 1, wherein the one or more NDR comprises at least two NDRs, optionally six NDRs, further optionally ten NDRs.
 11. The method according to claim 1, wherein the total length of the one or more NDR is no more than 30 kb.
 12. The method according to claim 1, wherein the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof.
 13. The method according to claim 1, wherein the method is a method of determining disease progression in a subject and the method further comprises: determining in a subsequent blood sample obtained from the subject, a level of cfDNA that maps to one or more NDR; estimating the ctDNA burden based on said level of cfDNA; comparing the ctDNA burden estimated from said subsequent blood sample with the ctDNA burden estimated from said blood sample; and identifying the subject as having disease progression if the ctDNA burden estimated from said subsequent blood sample is higher than the ctDNA burden estimated from said blood sample and identifying otherwise if the ctDNA burden estimated from said subsequent blood sample is not higher than the ctDNA burden estimated from said blood sample.
 14. The method according to claim 13, the method further comprising changing the treatment regimen received by the subject if the subject is identified as having disease progression.
 15. The method according to claim 1, wherein the tumor comprises colorectal tumor.
 16. The method according to claim 15, wherein the one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.
 17. A kit for estimating a ctDNA burden in a subject, the kit comprising one or more probe that is capable of binding to one or more NDR, wherein said NDR (i) comprises the NDR of a gene which transcript is differentially expressed between healthy blood sample and tumor sample and/or (ii) is degraded to different extents between cfDNA in healthy blood sample and cfDNA in blood sample of a tumor-bearing subject.
 18. The kit according to claim 17, wherein said one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SLC11A1, NLRP12, PRTN3, HMBS, LILRB3, ACSL1, GP9, MX2, RASGRP4, ATG16L2 and combinations thereof.
 19. The kit according to claim 17, wherein said tumor comprises colorectal tumor and wherein said one or more NDR comprises one or more NDR of a gene selected from the group consisting of: SHKBP1, ACSL1, BCAR1, RAB25, PRTN3, LSR and combinations thereof.
 20. The kit according to claim 19, wherein the one or more probe comprises the sequence of one or more of SEQ ID NO: 1 to SEQ ID NO: 577, or a sequence sharing at least 75% sequence identity thereto. 